Week 10 arrives with a wave of injuries across the NFL, creating chaos for some teams and opportunities for others to step up. For example, the Giants will be without RB Cam Skattebo, who’s sidelined with an ankle injury. In his absence, Tyrone Tracy Jr. may take on an expanded role, giving him a chance to make a fantasy impact.
Star Texans QB C.J. Stroud has been ruled out (concussion), which means Davis Mills will take over as the team looks to keep its offense afloat. Meanwhile, in New York, the Jets may finally get a spark as reports indicate WR Garrett Wilson is trending toward playing after missing time with injury.
Out west, QB Brock Purdy’s status remains uncertain, with the 49ers potentially leaning on Mac Jones again if Purdy can’t go. In New Orleans, the Saints appear committed to giving rookie QB Tyler Shough another start as he continues to settle into the offense.
Week 10 is shaping up to be a pivotal one as backups and emerging playmakers are thrust into the spotlight, creating new fantasy dynamics across the slate. This week offers a perfect blend of injury-driven value and exploitable mismatches.
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NFL Week 10 Predictions & Cheat Sheet for PrizePicks, NFL DFS
Find the top Week 10 predictions, picks, matchups to target, and players to target below in the PrizePicks Cheat Sheet.
Best RB Matchups to Target: Week 10
Bills RB James Cook vs. Dolphins Defense
Bills RB James Cook is in the midst of a breakout season and has emerged as one of the NFL’s most explosive rushers. He ranks second in the league in explosive runs, first in yards per carry (5.7), second in rushing yards (867), and fourth in rushing TDs (7). His combination of burst and vision has made him the engine of the Bills’ offense.
Cook now faces a Dolphins defense that has been gashed on the ground. Miami is allowing 145.6 rushing yards per game (30th in the NFL) and 5.0 yards per carry (27th). The Dolphins also rank 31st in yards after contact per carry, surrendering a total of 692 yards after contact.
With Miami’s front seven struggling to contain explosive backs, Cook might be set up for another huge performance.
Week 10 PrizePicks Pick: James Cook 84.5 Rushing Yards
Bears RB Kyle Monangai vs. Giants Defense
Rookie RB Kyle Monangai made a national statement last week, torching the Bengals for 176 rushing yards while filling in for the injured D'Andre Swift. Despite limited overall volume (68 carries), Monangai already ranks top-28 in rushing yards (362) and top-five in yards per attempt (5.3), showing exceptional efficiency and burst. He’s also recorded nine explosive runs, proving to be a big-play threat.
The matchup this week is favorable once again, as the Giants’ run defense has been one of the league’s worst. They’re allowing 150 rushing yards per game (31st in the NFL), 5.7 yards per carry (dead last), and have given up 12 rushing TDs to RBs (fifth-most).
If Monangai maintains his current form, he could post another statement game against one of the softest run-stopping units in football.
Best WR vs. CB Matchups to Target: Week 10
Bears WR Rome Odunze vs. Giants CB Deonte Banks
The Giants’ secondary continues to be a glaring weakness, and former first-round CB Deonte Banks has been one of the biggest disappointments in coverage. Banks ranks 104th out of 109 cornerbacks in Pro Football Focus' coverage grade and has been routinely exposed by opposing receivers. When targeted, he’s allowing a dreadful 158.0 passer rating and 14.7 yards per reception.
On the other side of this matchup, Bears WR Rome Odunze has emerged as one of the most efficient young receivers in football. He’s averaging 7.4 targets and 4 receptions per game, producing nearly 60 yards per contest and a 15.3 yards-per-catch clip. When targeted, Odunze carries a 90.8 passer rating, and his five TDs rank inside the top 10. His 473 yards on 56 targets are both top-25 marks.
Against a struggling corner like Banks, Odunze has a prime opportunity to continue his breakout campaign.
Week 10 PrizePicks Pick: Rome Odunze 54.5 Receiving Yards
Dolphins WR Jaylen Waddle vs. Bills CB Christian Benford
The Bills' defense remains strong overall, but its secondary has shown cracks, particularly with CB Christian Benford. Benford has allowed a 126.3 passer rating and 11.9 yards per reception when targeted — numbers that make him perhaps the most vulnerable piece of Buffalo’s defense.
With WR Tyreek Hill sidelined, Jaylen Waddle stepped into a clear WR1 role and has flourished with the extra volume. Over his last five games, he's averaging 7.2 targets and has hauled in 6+ receptions in three of those contests. He ranks top 15 in receiving TDs and top 10 in receiving yards (586) while generating a 111.7 passer rating when targeted.
Waddle’s speed and precision route running make him a nightmare matchup for Benford. With Hill out, he could be positioned for another high-volume, high-ceiling performance.
Week 10 PrizePicks Pick: Jaylen Waddle 65.5 Receiving Yards
Best OL/DL Matchups to Target: Week 10
Browns DL vs. Jets OL
The Jets' offensive line has been an ongoing liability. Former first-round pick Olu Fashanu has struggled transitioning to the NFL, allowing 22 pressures, 3 sacks, and drawing 3 penalties. LG John Simpson has surrendered 17 pressures and 3 sacks, while committing 5 penalties across 510 snaps. On the right side, RG Joe Tippmann has been equally shaky, allowing 18 pressures and 5 sacks while drawing 4 penalties in just 512 snaps.
Lined up across from them is arguably the best pass rusher in the NFL, DE Myles Garrett. Garrett has posted 34 total pressures, 11 sacks (most in the league), and 19 quarterback hurries despite being the focal point of every offensive line.
Fellow DE Alex Wright is thriving with 3 sacks, 4 hurries, and 7 total pressures on just 138 pass-rush snaps. Up the middle, interior lineman Maliek Collins has recorded 4 sacks (sixth-most among DTs) and 20 hurries, making this Browns front one of the most disruptive in football.
Dolphins OL vs. Bills DL
The Dolphins' offensive line continues to be a glaring weakness, particularly in pass protection. Rookie LT Patrick Paul has allowed 11 pressures, 2 sacks, and drawn an eye-popping 14 penalties. On the opposite edge, RT Larry Borom has surrendered 15 pressures and 2 sacks, along with 5 penalties. RG Cole Strange has also underperformed, giving up 12 pressures, 1 sack, and committing a penalty.
This struggling unit will have its hands full against a loaded Bills pass rush. Offseason acquisition Joey Bosa ranks fourth out of 105 edge defenders in pass rush grade, via PFF. He has accumulated 35 pressures (12th in the NFL) and 9 QB hits (seventh).
On the opposite side, Greg Rousseau is quietly producing with 27 pressures and 4 sacks. Interior lineman DaQuan Jones adds interior juice, logging 10 pressures and 2 sacks in just 108 pass-rush snaps.
Week 10 PrizePicks Pick: Tua Tagovailoa 221.5 Pass Yards
Best QB Matchups for Week 10
Matthew Stafford vs. 49ers Defense
The 49ers' defense, once among the most dominant in the league, has been riddled with injuries and inconsistency. As a result, they now rank 23rd in the NFL in EPA/pass, per SumerSports, and have struggled to generate consistent pressure. Their secondary has also been vulnerable, particularly S Malik Mustafa, who’s allowing a 116.7 passer rating when targeted and giving up 17.8 yards per reception.
Veteran QB Matthew Stafford continues to defy time and expectations, delivering one of the most efficient starts of his long career. The former No. 1 pick ranks third in passing yards (2,147), first in passing TDs (21), and has thrown just two INTs all year.
With San Francisco’s pass rush diminished and its coverage leaking big plays, Stafford may have ample time in the pocket.
Week 10 PrizePicks Pick: Matthew Stafford 261.5 Passing Yards
Jared Goff vs. Commanders Defense
The Commanders’ secondary has been a disaster, and things just got worse. Veteran CB Marshon Lattimore suffered a season-ending ACL tear, leaving a group that already ranked 29th in the NFL in EPA/dropback even more vulnerable.
Much of Washington’s defensive collapse stems from S Quan Martin, who ranks 76th out of 86 safeties in coverage, per PFF. When targeted, Martin has allowed a 144.4 passer rating and an alarming 21 yards per reception. On the outside, CB Trey Amos hasn’t been much better. He’s surrendering a 105.2 passer rating and 14 yards per reception, giving opposing QBs easy deep-ball opportunities.
That’s bad news heading into a matchup with QB Jared Goff, who has been quietly putting together another strong season under center for Detroit. Goff ranks top 15 in passing yards (1,915) and third in the NFL in passing TDs (17), showing impressive command of the Lions’ offense.
With Washington’s secondary in shambles, Goff might have no problem continuing his efficient, high-volume passing attack.
Week 10 PrizePicks Pick: Jared Goff 250.5 Passing Yards
Play NFL DFS on PrizePicks in Week 10
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