The Week 10 NFL schedule for the 2021 season is stacked with great matchups, and we’ve got you covered with what you need to know heading into the weekend. Our NFL Nation reporters bring us the biggest keys to every game, a bold prediction for each matchup and, of course, final score picks.
Additionally, ESPN Stats & Information provides a big stat to know and a betting nugget for each contest, and our Football Power Index (FPI) goes inside the numbers with a matchup rating (on a scale of 1 to 100) and a game projection. ESPN researcher Kyle Soppe hands out helpful fantasy football tips as well. Everything you want to know is here in one spot to help you get ready for a loaded weekend of NFL football.
Let’s get into the full Week 10 slate, including a red-hot Titans defense facing Alvin Kamara and the Saints, Chase Young chasing after Tom Brady, the potential returns of Russell Wilson and Aaron Rodgers and a big AFC West matchup between the Chiefs and Raiders on Sunday night. It all culminates with a Monday Night Football matchup between the Rams and the 49ers on ESPN. (Game times are Sunday unless otherwise noted.)
Jump to a matchup:
CLE-NE | NO-TEN | TB-WSH
BUF-NYJ | ATL-DAL | JAX-IND
DET-PIT | MIN-LAC | CAR-ARI
SEA-GB | PHI-DEN | KC-LV
Thursday: MIA 22, BAL 10
Bye: CHI, CIN, NYG, HOU
1 p.m. ET | CBS
Matchup rating: 67.5 | Spread: NE -2.5 (45)
What to watch for: The Patriots have relied on the run game in recent weeks, averaging 137.4 yards over their past five games and helping take some pressure off rookie quarterback Mac Jones. But running on the Browns might be their greatest challenge, as the Cleveland defense allows the NFL’s third-fewest rushing yards (84.8) and second-fewest yards per rush (3.5). So it might come down to Jones’ ability to throw it in the critical situations. — Mike Reiss
Bold prediction: One week after Cleveland cornerback Denzel Ward’s 99-yard pick-six, the Browns will score another defensive touchdown. That will prove to be the difference in a nail-biter. The Patriots’ 14 turnovers are tied for sixth in the NFL. — Jake Trotter
Stat to know: New England has played man coverage at the fifth-highest rate in the NFL this season, according to ESPN metrics and NFL Next Gen Stats (57%). And on those looks, the Patriots have produced an NFL-high nine interceptions and kept opposing QBs to a 43 QBR (seventh lowest). Browns quarterback Baker Mayfield, meanwhile, has struggled against man coverage this year. His 29 QBR against that scheme is the second worst in the NFL, putting him ahead of only Zach Wilson.
Injuries: Browns | Patriots
What to know for fantasy: Browns running back Nick Chubb is on pace to be the seventh player to have 1,500 rushing yards on fewer than 300 carries in a season. Last week was his third top-10 finish at the position this year. See Week 10 rankings.
Betting nugget: New England has gone over the total in four straight games after going under the total in its first four. Read more.
Trotter’s pick: Browns 22, Patriots 21
Reiss’ pick: Patriots 23, Browns 20
FPI prediction: NE, 56.4% (by an average of 2.2 points)
Matchup must-reads: Sources: Browns’ Chubb tests positive for COVID … Three decades since stint as Browns coach, Belichick is still evolving … Browns sign Teller to 4-year, $56.8M extension … Belichick reflects on how Patriots have turned season around … Browns agree to 3-year extension with LG Bitonio
1 p.m. ET | CBS
Matchup rating: 65.2 | Spread: TEN -3 (44)
What to watch for: The Saints’ run defense is the best in the league, allowing only 73.8 yards per game. But Titans offensive coordinator Todd Downing wants to maintain the same run-heavy approach they’ve had this season. The way the carries are distributed and how much patience the Titans have with the run game is something to watch, because the rushing attack is critical in setting up the play-action passing part of Tennessee’s offense. — Turron Davenport
Bold prediction: Saints backup quarterback Taysom Hill will throw and run for touchdowns while reemerging as a dynamic playmaker for a Saints offense in dire need of them. Surprisingly, he has never had a passing and rushing score in the same game. But Titans receivers A.J. Brown and Julio Jones will both find the end zone as well. — Mike Triplett
Stat to know: Titans running back Adrian Peterson needs one TD to pass Walter Payton (125) and tie Jim Brown (126) for 10th on the all-time list. New Orleans running back Alvin Kamara, meanwhile, is seeking his fifth straight game with a trip to the end zone, which would be his longest streak within a season since 2018.
Field Yates and Matthew Berry rate the performances of Jeremy McNichols and Adrian Peterson on Sunday night.
Injuries: Saints | Titans
What to know for fantasy: In the last 10 quarters of Derrick Henry’s season, Brown turned 29 targets into 25 catches, 379 yards and two scores. In the first week without him, Brown’s 11 targets yielded just five catches and 42 yards. See Week 10 rankings.
Betting nugget: Since 2018, New Orleans is 7-1 against the spread (ATS) as a road underdog. Read more.
Triplett’s pick: Titans 24, Saints 23
Davenport’s pick: Titans 24, Saints 17
FPI prediction: TEN, 59.7% (by an average of 3.4 points)
Matchup must-reads: Quarterback wasn’t Saints’ problem in first loss without Winston … Peterson scores 125th career TD
1 p.m. ET | Fox
Matchup rating: 61.4 | Spread: TB -9.5 (51)
What to watch for: Washington quarterback Taylor Heinicke played better against the Bucs’ defense than almost any other QB in last season’s playoffs. He completed 26 of 44 passes for 289 yards, one touchdown and an interception but also ran six times for 46 yards and another score in a 31-23 loss. But Tampa wasn’t expecting to face him last January and now has eight more games of film to study him. — John Keim
Bold prediction: Buccaneers quarterback Tom Brady will throw at least four touchdown passes. That might seem routine for him — he has five such games this season — but he could potentially be without tight end Rob Gronkowski and receivers Antonio Brown, Scotty Miller and Chris Godwin, depending on the status of Godwin’s ankle injury. Washington has given up 286.8 passing yards per game this year (most in the NFL) and 20 passing touchdowns (second most), while Tampa Bay receiver Mike Evans put up 119 receiving yards against this group last season. He should have a big day, but the Bucs will need guys like Tyler Johnson, Cameron Brate and O.J. Howard to continue stepping up. — Jenna Laine
Stat to know: Evans’ six receiving touchdowns since Week 5 are the most in the NFL.
Injuries: Buccaneers | Washington
What to know for fantasy: The Bucs have had one of the top six receivers in fantasy in each of their past four games, and they twice had two receivers crack the top six in a given week over that stretch. See Week 10 rankings.
Betting nugget: Washington is 1-7 ATS overall, the worst mark in the NFL. Read more.
Laine’s pick: Buccaneers 35, Washington 21
Keim’s pick: Buccaneers 31, Washington 20
FPI prediction: TB, 77.7% (by an average of 10.3 points)
Matchup must-reads: Injuries, penalties biggest road blocks in Buccaneers’ quest to win another title … Washington is 2-6 again, but this hole seems much deeper
1 p.m. ET | CBS
Matchup rating: 51.7 | Spread: BUF -12 (47.5)
What to watch for: On paper, this is a get-right game for the Bills, who don’t look like a Super Bowl contender at the moment. They have dropped two out of three, including an inexplicable loss to the Jaguars. Have no fear, Bills Mafia, the Jets are what you need. New York’s defense is ranked 32nd in points against (31.4 per game) and yards allowed (408.1 per game) — both franchise worsts. — Rich Cimini
Bold prediction: Buffalo running back Devin Singletary will run for 75-plus yards, and the Bills’ running game will take a step in the right direction. Singletary has seen his carries decrease over the past few games and has not run for even 30 yards since Week 4. But with fellow running back Zack Moss in concussion protocol this week and coach Sean McDermott publicly discussing how the team’s rushing attack needs to be better, Singletary will have an opportunity for a big game. The fact that the Jets have the sixth-worst rushing defense (133.3 yards against per game) and are tied for the league high in 15 rushing touchdowns allowed will only help the Bills prove they can run the ball. — Alaina Getzenberg
Stat to know: Jets quarterback Mike White has a 60.4 Total QBR this season. The only Jets QB to have 60-plus QBR in the past 15 seasons was Ryan Fitzpatrick, who had a 62.0 in 2015 (min. 100 action plays).
Injuries: Bills | Jets
What to know for fantasy: A different Bills wide receiver has scored over 21 fantasy points in each of Buffalo’s past four games on the road against the Jets: Deonte Thompson, Zay Jones, John Brown and Cole Beasley. See Week 10 rankings.
Field Yates and Daniel Dopp look at the highs and lows of Josh Allen’s fantasy season and discuss what it means for fantasy managers.
Betting nugget: New York has won its past two home games as at least a six-point underdog outright. Read more.
Getzenberg’s pick: Bills 27, Jets 13
Cimini’s pick: Bills 21, Jets 20
FPI prediction: BUF, 82.8% (by an average of 12.7 points)
Matchup must-reads: What went wrong with the Bills’ offense, and can it be fixed? … Jets make right call on quarterbacks but could be playing with fire … How to explain Jets’ surge on offense? QB change among top factors
1 p.m. ET | Fox
Matchup rating: 51.5 | Spread: DAL -9.5 (55)
What to watch for: The Cowboys are coming off their worst performance of the season in a loss to Denver, while the Falcons surprised New Orleans last week and have won three of four games. How will each team react? A year ago, the Cowboys beat Atlanta but needed help from an onside kick to get there. Dallas quarterback Dak Prescott has thrown multiple touchdown passes in five straight games but was off in his return from a calf injury vs. the Broncos. The Cowboys need Prescott and the offense to find their form to help their defense against Falcons quarterback Matt Ryan. — Todd Archer
Bold prediction: Former Falcons head coach Dan Quinn is facing his old team as Dallas’ defensive coordinator — and it’s going to be a long day. The Falcons and Cowboys will combine to put up over 800 yards of offense in a true display of offensive fireworks from both teams. Ryan and Prescott will also each have 300-yard passing days with three touchdowns apiece. — Michael Rothstein
Stat to know: In four home games this season, Dallas receivers CeeDee Lamb and Amari Cooper have combined for 94.5 receiving yards per game and three touchdowns, as opposed to 196.5 receiving yards per game and six TDs in four road games. Neither Lamb nor Cooper has a 100-yard game at home in 2021.
Injuries: Falcons | Cowboys
What to know for fantasy: Falcons tight end Kyle Pitts had 51.6% of his season yardage (and his only score) during a two-week stretch against struggling AFC East opponents (Dolphins and Jets). See Week 10 rankings.
Betting nugget: Dallas is 7-1 ATS this season but is coming off its first noncover of the season. Still, Dallas is 5-0 ATS in conference games. Read more.
Rothstein’s pick: Cowboys 38, Falcons 31
Archer’s pick: Cowboys 31, Falcons 26
FPI prediction: DAL, 74.9% (by an average of 9.0 points)
Matchup must-reads: In finding ways to win close games, Falcons may have discovered their identity … Cowboys DE Gregory (calf) out multiple weeks … Cowboys’ Lamb confused by NFL’s ‘weird’ fines … Quinn’s defense has more to fix, but he’s remade himself with Cowboys
1 p.m. ET | CBS
Matchup rating: 39.9 | Spread: IND -10.5 (47.5)
What to watch for: How will the Jaguars slow the Colts’ run game? Yes, Indianapolis running back Jonathan Taylor rushed for a career-high 253 yards against the Jaguars in the season finale in 2020. But it’s not about that. It’s about Taylor having rushed for at least 107 yards in four of the past six games. The Jaguars aren’t bad when it comes to stopping the run — 103.4 yards allowed per game — but the Colts are leaning more on the run, as they’re fifth in the league with 137.4 yards per game. — Mike Wells
Bold prediction: Taylor will rush for fewer than 60 yards. He is coming off a 172-yard performance against the Jets, but the Jaguars are allowing only 3.8 yards per carry (third in the NFL) and 103.4 yards per game rushing. Jacksonville has struggled against the pass but has been solid against the run, so Taylor is going to have a tough day. — Mike DiRocco
Stat to know: Jaguars quarterback Trevor Lawrence is averaging 302.5 passing yards and two TD throws over a pair of divisional matchups this season. In nondivision games, he averages 100 fewer passing yards (202.7) and has just four passing TDs in six games.
Injuries: Jaguars | Colts
What to know for fantasy: Colts quarterback Carson Wentz has six games with two passing touchdowns and no interceptions, tied with Aaron Rodgers for the most this season. See Week 10 rankings.
Field Yates explains why Carlos Hyde can be a worthwhile fantasy football pickup this week.
Betting nugget: Jacksonville is 10-1-1 ATS in the past 12 meetings between these teams — with three straight covers. Read more.
DiRocco’s pick: Colts 17, Jaguars 14
Wells’ pick: Colts 31, Jaguars 17
FPI prediction: IND, 78.2% (by an average of 10.5 points)
Matchup must-reads: Is Jaguars’ upset of Bills a sign things have turned or just a lucky day? … Taylor dominates to help Colts run past the Jets
1 p.m. ET | Fox
Matchup rating: 26.2 | Spread: PIT -9 (42.5)
What to watch for: The Steelers have a bad habit of letting teams hang around in the second half, and just earlier this week, they allowed the Bears to mount a two-score comeback to take the lead in the fourth quarter. Coach Mike Tomlin was adamant there aren’t any FCS games in the NFL, and facing a winless Lions team, the Steelers will have to ward off second-half complacency to avoid falling victim to a team whose desperation makes it especially dangerous. — Brooke Pryor
Bold prediction: Lions quarterback Jared Goff will pass for 300 yards. He has seven straight starts with under 300 passing yards, which is tied for the longest streak in the NFL this season. He has averaged a league-low 6.1 air yards per attempt, but part of that has to do with his offensive weapons, particularly at wide receiver. Regardless, Goff is coming off a bye week where he said he had a lot of time to refresh. This will be the week that he breaks the streak. — Eric Woodyard
Stat to know: Steelers running back Najee Harris has 752 scrimmage yards on the year, the most by any Steelers player in his first seven career games since the 1970 merger.
Injuries: Lions | Steelers
What to know for fantasy: Don’t let the bye week make you forget that Detroit running back D’Andre Swift is on pace for 100 receptions this season. He has caught at least five passes in four straight games. See Week 10 rankings.
Betting nugget: Pittsburgh has failed to cover eight straight times as a favorite, including the playoffs. It went 3-5 outright in that span. Read more.
Woodyard’s pick: Steelers 26, Lions 20
Pryor’s pick: Steelers 27, Lions 23
FPI prediction: PIT, 73.6% (by an average of 8.5 points)
Matchup must-reads: Lions have best odds to land No. 1 overall pick in 2022 … Steelers’ Tomlin supporter of taunting penalty
4:05 p.m. ET | Fox
Matchup rating: 60.5 | Spread: LAC -3 (53)
What to watch for: Can Chargers quarterback Justin Herbert build off his big game in Philly? After two straight mediocre performances in losses to the Ravens and Patriots, Herbert completed 32 of 38 passes (84.2%) for 356 yards in the win over the Eagles. (Chargers coach Brandon Staley said Herbert was actually upset about the six incompletions, despite the terrific outing.) Now the second-year QB is poised to have another big game against the Vikings. — Shelley Smith
Bold prediction: Vikings running back Dalvin Cook will have north of 100 yards rushing and two touchdowns. The Chargers have the NFL’s worst run defense (5.0 yards allowed per rush) and have given up 11 scores on the ground. Cook, who is maintaining his innocence in response to allegations of assault in a civil lawsuit filed against him this week, say he expects to play. He has an opportunity to post his fourth 100-yard game of the season. It is also an opportunity for Minnesota to get rookie Kene Nwangwu some touches on offense by utilizing his speed and quickness in the run game. — Courtney Cronin
Stat to know: Vikings quarterback Kirk Cousins has zero interceptions in seven straight road games, the longest active streak by a starting QB. The last quarterback to go at least eight straight road starts without one was Tom Brady from 2020 to 2021 (nine straight).
Injuries: Vikings | Chargers
What to know for fantasy: Chargers receiver Mike Williams has 16.4 total fantasy points over the past three weeks. Prior to that stretch, he was averaging 23.2 fantasy points per game this season. See Week 10 rankings.
Mike Clay and Field Yates look at what challenges Mike Williams faces against the Vikings in Week 10.
Betting nugget: Minnesota has played seven one-score games — the most in the NFL — including three overtime games and four games decided by three or fewer points. Read more.
Cronin’s pick: Chargers 27, Vikings 24
Smith’s pick: Chargers 34, Vikings 31
FPI prediction: LAC, 58.9% (by an average of 3.1 points)
Matchup must-reads: Vikings’ Cook says ‘truth will come out’ on lawsuit accusing RB of assault … How Herbert is navigating second-year ups and downs
4:05 p.m. ET | Fox
Matchup rating: 53.1 | Spread: ARI -10.5 (44)
What to watch for: All eyes will again be on the Cardinals’ quarterback. Will it be Kyler Murray or Colt McCoy? Murray is still recovering from a sprained left ankle, and even though he feels much better this week than last, his status for Sunday is still day-to-day. The Cardinals showed last week that they can win — and win easily — with McCoy. Can they do it again with him, or will Murray return and lead Arizona to a 9-1 record? — Josh Weinfuss
Bold prediction: The Cardinals will sack Panthers quarterback P.J. Walker six times and force him into three interceptions behind an offensive line that has only one starter at the same position he began the season (right tackle Taylor Moton). The line is a mess and Walker tends to take too many chances. He’s playing against a defense ranked fourth in sacks (25) and third in takeaways (17). — David Newton
Stat to know: Panthers running back Christian McCaffrey has 100-plus scrimmage yards in three of the four games he has played, and his 117.5 scrimmage yards per game is the third highest in the NFL. McCaffrey played 47% of the offensive snaps last week in his return from a hamstring injury.
Injuries: Panthers | Cardinals
What to know for fantasy: Cardinals running backs James Conner and Chase Edmonds have been top-20 running backs in the same week twice this season and top-30 backs in the same week four times. In the short term, this is Conner’s backfield with Edmonds nursing an ankle sprain. Conner’s 10 rushing TDs are tied for the most in the NFL (Derrick Henry). See Week 10 rankings.
Betting nugget: Arizona is 7-2 ATS this season and 6-1 ATS in its past seven games, but Carolina is 9-3 ATS in road games under coach Matt Rhule. Read more.
Newton’s pick: Cardinals 32, Panthers 13
Weinfuss’ pick: Cardinals 38, Panthers 17
FPI prediction: ARI, 85.2% (by an average of 14.1 points)
Matchup must-reads: Panthers’ Reddick proving he is ‘one of the best edge-rushers in this game’ … Murray feels ‘way better,’ eyes Sunday return … How Watt made WWII veteran and Chicago Cardinals star Marshall Goldberg relevant again … Source: Cards’ Edmonds has high ankle sprain … Newton signs deal to rejoin Panthers
4:25 p.m. ET | CBS
Matchup rating: 73.3 | Spread: GB -3.5 (49.5)
What to watch for: All eyes will be on the quarterbacks: Seattle’s Russell Wilson in his return from finger surgery and whether it’s Aaron Rodgers or Jordan Love for the Packers. The Packers won’t know until late Saturday whether Rodgers will check out OK after spending 10 days on the COVID list — and if he does play, how will the long layoff impact his performance? — Rob Demovsky
Bold prediction: The Seahawks’ defensive improvement will continue with at least three sacks of Rodgers (or Love). That qualifies as bold given how underwhelming their pass rush has been so far and how quickly Rodgers can get rid of the ball. Seattle is near the bottom of the NFL in sacks per dropback but showed some encouraging signs against Jacksonville. And assuming he plays, Rodgers’ timing might be off after a bout with COVID-19 and a 10-day absence. — Brady Henderson
Stat to know: With Wilson on the field this season, the Seahawks are averaging 6.5 yards per play and have a 59.5 QBR. But without him, they are averaging 4.7 yards per play and have posted a 44.3 QBR.
Injuries: Seahawks | Packers
What to know for fantasy: In six of eight games this season, one of DK Metcalf or Tyler Lockett has been a top-12 receiver. Both Seahawks receivers got there in Week 8 ahead of their bye and look to build on that production against the Packers on Sunday. See Week 10 rankings.
Matthew Berry reacts to Aaron Jones performance in the Packers’ loss to the Chiefs.
Betting nugget: Green Bay is 3-0 ATS at home this season and 4-0 ATS against teams with losing records. Read more.
Henderson’s pick: Packers 22, Seahawks 21
Demovsky’s pick: Packers 23, Seahawks 20
FPI prediction: GB, 54.9% (by an average of 1.7 points)
Matchup must-reads: Seahawks’ defense has improved, but matchup with Rodgers likely looms … Packers, Rodgers, Lazard fined for COVID-19 protocol violations, source says … Seahawks’ Wilson ‘looks pretty good’ at practice
4:25 p.m. ET | CBS
Matchup rating: 49.8 | Spread: DEN -2.5 (45.5)
What to watch for: The Eagles have rushed at least 30 times in four games this season, including two of their three wins. That identity gives quarterback Jalen Hurts the best chance to keep the offense moving. Will Philly stick with it against Denver? The Broncos are coming off their best-constructed win since Peyton Manning retired — 30-18 over Dallas last week — but they haven’t always handled their successes well (their 3-0 start was followed by a four-game losing streak). A win here would put them into their bye week at 6-4 and in the postseason conversation. — Jeff Legwold
Bold prediction: The Eagles’ defense will seal an upset win with a strip sack. Quarterbacks have been getting the ball out quick against the Eagles, in part because of the soft coverage on the back end. Things will tighten up Sunday, allowing the defensive linemen to take advantage of a banged-up Denver front and chase down quarterback Teddy Bridgewater, who is third in the NFL with 26 sacks against. Defensive end Derek Barnett will make amends for a costly penalty in the loss to the Chargers last week with a big performance. — Tim McManus
Stat to know: Philadelphia receiver DeVonta Smith has 537 receiving yards this season, the third most among rookies. He is looking to become the third Eagles rookie to record 600 receiving yards in his first 10 career games since the merger (DeSean Jackson in 2008 and Charle Young in 1973).
Injuries: Eagles | Broncos
What to know for fantasy: For the third time in four weeks, both Javonte Williams and Melvin Gordon returned top-30 value at the position. The fantasy community wants one to separate, but both Broncos running backs might well be usable, even in a timeshare. See Week 10 rankings.
Betting nugget: Denver games are 7-2 to the under this season, including three straight unders. Read more.
McManus’ pick: Eagles 20, Broncos 19
Legwold’s pick: Broncos 26, Eagles 17
FPI prediction: DEN, 63.5% (by an average of 4.7 points)
Matchup must-reads: Eagles, Hurts more dangerous with new run-heavy offensive identity … Are the Broncos positioning themselves for a QB this offseason? … How the Broncos’ defense looks without Miller
8:20 p.m. ET | NBC
Matchup rating: 55.9 | Spread: KC -2.5 (52)
What to watch for: Two of the game’s best tight ends — Kansas City’s Travis Kelce and Las Vegas’ Darren Waller — face off on Sunday night. Kelce, a six-time Pro Bowler and three-time first-team All-Pro, is looking for his third straight game against the Raiders with at least eight catches, 100 yards and a TD. He is averaging 108.0 receiving yards in his past four games against the Raiders. Waller, who set a franchise record with 107 catches last season, is looking to catch a TD pass in his third straight game against the Chiefs — and he has four TDs in his past five games against the AFC West. — Paul Gutierrez
Bold prediction: Kelce will catch a couple of touchdown passes. The Raiders have allowed a 75% completion percentage and 95.1 QBR when the tight end has been the target. Kelce has generally fared well against the Raiders, including two 100-plus-yard games last season. — Adam Teicher
Stat to know: The Raiders are allowing the second-fewest yards per attempt (6.3) in the NFL this season behind the Bills, and Chiefs quarterback Patrick Mahomes is throwing for 6.0 yards per attempt since Week 5 (No. 31 out of 34 qualified QBs over that span).
Injuries: Chiefs | Raiders
What to know for fantasy: Las Vegas receiver Hunter Renfrow has been a top-27 WR in four of his past six games, yet he was started in under half of ESPN leagues in Week 9 (43%). See Week 10 rankings.
Field Yates and Daniel Dopp evaluate Tyreek Hill’s play this season compared to what we’ve normally seen from him.
Betting nugget: Kansas City is 4-16 ATS in its past 20 games, including the postseason. Read more.
Teicher’s pick: Chiefs 24, Raiders 20
Gutierrez’s pick: Chiefs 35, Raiders 31
FPI prediction: KC, 52.6% (by an average of 1.0 points)
Matchup must-reads: Speed is the ‘easy answer’ when describing Chiefs’ Hill … Jackson not asking to get the ball 100 times for Raiders … Raiders cut former first-round CB Arnette after video with threats
Monday, 8:15 p.m. ET | ESPN
Matchup rating: 75.0 | Spread: LAR -4 (49)
What to watch for: The 49ers’ defense just got torched by Arizona’s backup offense, so what’s going to happen against a loaded and presumably angry Rams offense coming off a disappointing loss? Considering that the Niners are 30th in the league in QBR allowed (88.6) and 31st in yards allowed per attempt (10.3) when opposing offenses use empty formations, and the Rams go empty more than any other team in the league, the Niners had better come up with some answers in a hurry. Otherwise, their best bet is winning a shootout, something they haven’t proved capable of this season. — Nick Wagoner
Bold prediction: Watch for the Rams to dial up the passing game and for quarterback Matthew Stafford — coming off his worst outing of the season — to pass for more than 350 yards and three touchdowns. The 49ers’ defense has defended the pass well (206.5 passing yards allowed per game, fourth-best in the NFL) but has allowed an average of 25.3 points per game (No. 25). Coach Sean McVay and the Rams have lost four straight to division-rival San Francisco, and their last meeting in 2020 ended with McVay publicly expressing his frustration with now former quarterback Jared Goff. McVay does not want to lose five straight to his friend Kyle Shanahan. — Lindsey Thiry
Stat to know: The 49ers have the second-worst pressure percentage in the NFL this season at 24.2%, while the Rams have allowed the third lowest (24%).
Injuries: Rams | 49ers
What to know for fantasy: Rams receiver Cooper Kupp has never scored more than 13.1 fantasy points against the 49ers. In his five career games against the divisional rival, he has just 15 catches, 117 yards and one touchdown to show for his 142 routes run. See Week 10 rankings.
Betting nugget: San Francisco is 0-4 ATS at home and 0-3 ATS in division games this season. Read more.
Thiry’s pick: Rams 32, 49ers 24
Wagoner’s pick: Rams 34, 49ers 20
FPI prediction: LAR, 60.1% (by an average of 3.5 points)
Matchup must-reads: Stafford among Barnwell’s top midseason MVP candidates … 49ers haven’t gotten much from rookie class … McGlinchey out for season with quad injury … Beckham Jr. brings star power, deep-threat capability to Super Bowl-hungry Rams