Running Back Matchups to Target for Week 17 (2025) - James Cook III, Saquon Barkley, More

Thunder Dan's favorite RB matchups to exploit for Week 17 of 2025 -- DFS running backs to target on DraftKings and FanDuel. These RB matchups are GPP and cash game opportunities.

The NFL season is winding down, and while your season-long team may (or may not) have been eliminated from the playoffs, you know that we are still grinding DFS and prop bets all the way to the end of the season and through the NFL playoffs, too!

This week's disclaimer is that you WILL NOT find Ashton Jeanty in this article, but that does not mean that he's not a top play by any means. He is, however, trending towards being one of the chalkiest plays of the season, with rostership projections that are pushing 50% for tomorrow's slate. Yeah, the Raiders' rushing attack has been bad all season, but we saw Jeanty erupt for some huge plays last week, and now he gets the league-worst rushing defense of the New York Giants. He's a must-play in cash games, but his matchup doesn't technically pop in my metrics as a top-5 spot, so I decided to roll with four OTHER backs in this article this week instead!

The primary focus of this piece is NFL DFS; however, these are also running backs you should consider adding to your season-long lineups and are great candidates for prop bets. We also have lots of great NFL DFS articles and NFL DFS tools to help you win MORE this season! Without any further ado, here are my top four matchups for the Week 17 main slate on Sunday, December 28th.

Week 17 Running Back Matchups

In my constant search for usable metrics, I crunched the first 15 weeks of data. The first column shows the overall offensive rushing attack vs. the opponent, calculated from each team's offensive and defensive DVOA.

The second column is the offensive vs. defensive line matchup, calculated from each team's "adjusted line yards" created and allowed. The third column is simply Pro Football Focus' run-blocking grade for each team's offensive line.

James Cook III ($8,000 DK, $9,000 FD)

Buffalo Bills vs. Philadelphia Eagles

If you read last week's piece and plugged Cook into some lineups, you probably won some money, as he had a huge day against Cleveland at a relatively low rostership - just as we expected! This is another situation where you can probably get Cook at a discount in terms of rostership this week, as the Eagles certainly don't show up as a top matchup for opposing backs.

But is the Bills' run game matchup proof at this point? Cook has gone for 100 yards now against the Browns, Texans, Chiefs, and Patriots this season - all teams with well-respected rush defenses. Philadelphia's defensive line has not been its strength this season, and opposing teams have found running room up the middle at times. Buffalo will certainly test them early in this one and will attempt to own the line of scrimmage and control this game.

This game has a relatively low total and tight spread - and a playoff game atmosphere. I expect both teams to try to run the football, play solid defense, and try to avoid turnovers. It's not a must-win for either team, but both teams certainly want this one to improve their playoff positioning and give themselves a chance to possibly rest some key players next week.

Saquon Barkley ($7,600 DK, $8,700 FD)

Philadelphia Eagles at Buffalo Bills

The Eagles are starting to get their mojo back, and Barkley, who had struggled for much of the first part of the season, has begun to find more holes to run through lately. He piled up 132 yards against Washington last week and had 122 against the Chargers two weeks before that. Philadelphia's patchwork offensive line is starting to gel a bit more and has looked better recently, and Barkley's recent surge in production reflects that.

Saquon spinning in slow-mo 😮‍💨 pic.twitter.com/e8Y0qUkooR

— Philadelphia Eagles (@Eagles) December 22, 2025

We know by now that opposing teams are going to go right at Buffalo's front seven and their 30th-ranked run defense. The formula for beating Buffalo is run the football, control the clock, and force Josh Allen and company to play from behind. Both teams will be trying to exert their will in this one, and I suspect whichever team establishes the run more effectively will win.

James Cook has the better run blockers in front of him, but I don't think many would argue that Barkley isn't the more elusive and powerful runner. He's one of my favorite plays this week, and I think he could be heading for another big day. Don't be surprised if he breaks a few tackles in the second level and takes a long run to the house.

Chase Brown ($7,400 DK, $8,000 FD)

Cincinnati Bengals vs. Arizona Cardinals

We can't really talk about this slate without acknowledging the Cincy-Arizona game that has a 53.5-point total and the potential to break the slate. The Cardinals and Bengals don't have anything to play for other than pride (and stats), and both defenses have been downright bad this year. When we get two pretty good offenses, two bad defenses, and a spread inside a touchdown (and maybe the fact that neither team has anything to lose, too), the potential for a shootout here is massive.

Brown saw a downtick in overall touches last week, ceding some work to Samaje Perine again for the second straight week. However, he was incredibly efficient with his 16 touches, turning them into over 100 scrimmage yards and three touchdowns.

Chase Brown hat trick!

CINvsMIA on CBS/Paramount+https://t.co/HkKw7uXVnt pic.twitter.com/HoRgvF5CDv

— NFL (@NFL) December 21, 2025

Arizona can be run on, and their run defense has actually been worse than their pass defense this year, especially in the second half of the season. Everyone is gearing up for a huge game from Joe Burrow and Ja'Marr Chase in this one, but Chase Brown could be the Bengal who has the clearest path to a huge game; it's just a matter of whether or not he gets those crucial red zone carries or targets.

The Cardinals' run defense has been a sieve, and Brown has been as good as any back in the league the last month and a half. I'll be overweight on him compared to the field for sure.

Michael Carter ($5,200 DK, $6,500 FD)

Arizona Cardinals at Cincinnati Bengals

On the other side of this game, we get Michael Carter against the Bengals and their 31st-ranked run defense. The Cardinals tend to be a pass-first offense, but Carter has only practice-squad player Corey Kiner for early down work now that Bam Knight's season is over.

Last week, Carter was quite effective as the lead back, turning 11 carries into 65 yards on the ground. Emeri Demercado mixed in for five carries and saw one target as his primary backup, while Kiner also had six carries. Oddly enough, all three backs only combined for three targets out of the backfield in this one.

There's no way to know how the touches will be allocated this week, but Carter should get the first crack at them and is the most likely to be the red zone and short-yardage back, too. If the Cards were wise, they'd throw him the ball out of the backfield, too, as the Bengals have been one of the worst teams against running backs as receivers this season, too.

He's not drawing much rostership as of right now, but Carter is a very cheap way to get exposure to an elite game environment. We've been targeting the Bengals' run defense all season and I don't think we need to stop now!

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