Week 10 NFL DFS Picks, Predictions & Top Matchups For Main Slate
Get ready for NFL Week 10 with our top DFS picks and key matchups to target on PrizePicks. This week, we’ll spotlight the best pass and run defenses to target on the Sunday main slate, plus four picks to help build your NFL DFS Lineups.
This full guide will help you start your Week 10 Lineup construction and get insights into the vulnerable defenses and matchups to target.
Use these picks to build your NFL Lineups on PrizePicks, the easiest way to play NFL DFS. Just pick more or less on at least two player projections like the ones below to get real money action on Sunday’s games.
If you're looking for more NFL DFS picks and analysis for Week 10, check out our Cheat Sheet, for key OL vs. DL matchups, TD scorer predictions, and more.
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NFL Week 10 Picks for DFS & PrizePicks
- NFL Week 10 Injury Report + Notes
- Week 10 Pass Defense to Target
- Week 10 Run Defenses to Target
- Week 10 DFS Picks
Week 10 NFL Injury Report
49ers RB Christian McCaffrey (Achilles) Nearing His Return
49ers RB Christian McCaffrey was designated to return from injured reserve Monday, potentially setting him up to take the field Week 10 against the Buccaneers. 49ers RB Jordan Mason aggravated his left shoulder injury in Week 8, but even if he is healthy following the 49ers bye week, he would be in line to cede carries to McCaffrey if the 49ers star running back makes his return.
Cowboys QB Dak Prescott (Hamstring) To Be Placed on IR
Cowboys QB Dak Prescott was forced out of his Week 9 matchup with the Falcons because of a hamstring injury that is likely going to land him on injured reserve. Replacing him at quarterback will be QB Cooper Rush, who came on to throw for 115 yards and a touchdown after Prescott got hurt.
To complicate matters for the Cowboys, WR CeeDee Lamb is considered week-to-week with a shoulder injury, putting his status in question for a Week 10 matchup with the Eagles. He was limited in Wednesday’s practice, which is a good sign. They did trade for WR Jonathan Mingo from the Panthers at the deadline, which could improve their WR corps if Lamb is out.
Eagles WR A.J. Brown (Knee) Considered Day-to-Day
The Eagles have their own injury issues, as WR A.J. Brown was forced out of Week 9 with a knee injury. Tests results came back clean on his knee, meaning that he has likely avoided a significant absence. He practiced in limited fashion on Wednesday, which is good news.
If he is unable to play against the Cowboys in Week 10, then Eagles WR DeVonta Smith would step into a leading role. He caught four of six targets for 87 yards and a touchdown last week. TE Dallas Goedert would also likely find himself with more targets.
Saints WR Chris Olave Suffers Another Concussion
It was a scary scene when Saints WR Chris Olave was sandwiched between two hits attempting to catch a pass against the Panthers on Sunday. He was carted off the field and diagnosed with yet another concussion. Since this is his second concussion of the season, it could be a while until he retakes the field.
With Saints WR Rashid Shaheed (knee) and Saints WR Bub Watson (ankle) on injured reserve, the Saints will likely continue to rely heavily on RB Alvin Kamara moving forward. The Saints are thin at receiver, with Mason Tipton the likely snap leader, with Cedrick Wison Jr. behind him.
Other NFL Week 10 Injuries for DFS
- Bills WR Amari Cooper and Bills WR Keon Coleman are both battling wrist injuries heading into their Week 10 matchup with the Colts. Cooper was unable to play in Week 9, but he was limited in Wednesday’s practice. Coleman suffered his injury late in that game against the Dolphins and could miss multiple weeks. Bills WR Khalil Shakir received seven targets last week and should remain busy if Cooper and/or Coleman can’t play.
- Falcons WR Drake London suffered a hip injury against the Cowboys in Week 9, but seems to have avoided a serious issue. He is currently listed as day-to-day. Falcons WR Darnell Mooney stepped up with London getting hurt last week, catching five of nine targets for 88 yards and one touchdown.
- Commanders RB Brian Robinson Jr. was unable to take the field against the Giants last week because of a hamstring injury. In his place, Commanders RB Austin Ekeler posted 83 total yards and a touchdown. Should Robinson sit out another game, Ekeler would once again assume a larger role.
- Titans QB Will Levis (shoulder) could make his return from a three-game absence with head coach Brian Callahan saying that Levis will increase his workload in practice this week. Titans QB Mason Rudolph has thrown four touchdown passes and four interceptions during his absence.
- Texans WR Nico Collins (hamstring) did not practice on Wednesday and has not been designated to return from IR. He looks unlikely to return this week, which means WR Tank Dell and TE Dalton Schultz should stay busy.
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NFL Week 10 Pass Defenses to Target
Jacksonville Jaguars Defense vs. Vikings
The way to exploit the Jaguars defense has been through the air. They are tied for the most passing touchdowns allowed (19) in the league and they have allowed the second-highest explosive pass percentage (15.87%), per 4for4 Fantasy Football.
The Jags will certainly have their hands full with Vikings WR Justin Jefferson, who has posted back-to-back games with at least 115 receiving yards.
PrizePicks Projections: QB Sam Darnold 254.5 Pass Yards / WR Justin Jefferson 94.5 Receiving Yards
Arizona Cardinals Defense vs. Jets
The Cardinals haven’t been as bad as the Jaguars, but they aren’t far behind them. They have the fifth-highest pass EPA per play allowed (0.15) in the league, per 4for4.
With Jets WR Davante Adams now in the fold, Jets QB Aaron Rodgers has arguably the best wide receiver duo in the league with Jets WR Garrett Wilson also still thriving.
PrizePicks Projections: Aaron Rodgers 234.5 Yards / Garrett Wilson 68.5 Receiving Yards
NFL Week 10 Run Defenses to Target
Indianapolis Colts Defense vs. Bills
Bills RB James Cook received just 10 carries against the Dolphins last week, which was his second-lowest mark of the season, as Ray Davis continues to mix in. After averaging 4.7 yards per carry last season, he has averaged 4.6 yards per carry this year.
This is a potential breakout spot for him against the Colts, who have allowed the fifth-highest explosive rush percentage (11.54%) in the league, per 4for4. The Bills should control this game and be able to keep the run game going.
PrizePicks Projections: James Cook 63.5 Rush Yards
Washington Commanders Defense vs Steelers
It’s no secret that the Steelers want to run a lot. Steelers RB Najee Harris has been given at least 17 carries in a game five times. Entering this matchup, he has posted three straight games with at least 102 rushing yards, and he looks as explosive as ever.
It would not be a surprise if he at least approaches 100 rushing yards again with the Commanders allowing the second-highest yards per carry (5.1) in the league. It’d be wise to keep the ball on the ground and keep Commanders QB Jayden Daniels off the field.
PrizePicks Projections: Najee Harris 64.5 Rush Yards
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Week 10 NFL DFS Picks
Broncos QB Bo Nix vs. Chiefs: 24.5 Rush Yards – More
The Broncos want to use QB Bo Nix in the running game. He has received at least five carries in all but one game this season, and consistently looks to escape the pocket and run. That has propelled him to rush for at least 25 yards in a game six times, including in three of his last four games.
The Chiefs have allowed 4.6 yards per carry to opposing quarterbacks, so there’s no reason for the Broncos to shy away from giving Nix the green light to scramble again.
Saints RB Alvin Kamara 37.5 Receiving Yards – More
The Saints are in trouble with their lack of options at wide receiver. Saints RB Alvin Kamara has already been targeted at least seven times in six straight games, so expect him to remain busy moving forward.
When Kamara faced the Falcons in Week 4, he caught seven of nine targets for 42 yards. Helping his cause for this rematch is that the Falcons are tied for the most receptions allowed to running backs (55) in the league.
Best TD Scorer Pick: Falcons RB Tyler Allgeier (Demon)
The Falcons are in a great spot to come away with a convincing victory against the Saints. The Saints have lost seven straight, just fired their head coach, and are hurting at wide receiver.
Their defense has also been a problem, allowing 25.4 points per game. They have given up 12 rushing touchdowns, which is tied for the third-most in the league.
Falcons RB Tyler Allgeier has received 11 carries inside the red zone the last four weeks, coming away with two touchdowns. He seems to be the preferred back once the Falcons are inside the five. Multiple carries inside the red zone could be coming his way again in this matchup.
Patriots QB Drake Maye vs. Bears: 0.5 INTs – More (Goblin)
The Bears have one of the best pass defenses in the league. They have more interceptions (7) than they have allowed passing touchdowns (5). Patriots QB Drake Maye has already had problems with turnovers, throwing two interceptions in two of his four games as a starter, with a total 9 turnover-worthy plays in three starts, per PFF.
In one of the games that he didn’t throw an interception, he only played 18 snaps before leaving with a concussion. Look for him to be picked off at least one time in this matchup.
Note: Goblin picks reduce your payout on PrizePicks, as they are easier projections to hit.
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Build Your Week 10 NFL DFS Lineup on PrizePicks
Despite four NFL teams being on a bye for Week 10, there are plenty of games to enjoy for NFL DFS. There is no better way to get in on the action than by building a team on PrizePicks for the Sunday main slate.
There are no salary constraints, so pick two or more projections for your favorite players, finalize your lineup, stay in the green, and get paid.
Follow Mike Barner for more NFL DFS Picks: @rotomikebarner
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