Patriots vs. Bills Prediction, Spread, NFL Picks Today – Sunday, October 4

In Week 4, the New England Patriots (1-2) will hit the road to take on the Buffalo Bills (3-0) at 1 p.m. ET on Sunday, October 4. The Bills come in as 6.5-point home favorites, and they would return a 1.29x payout if they win outright, per PrizePicks.

The vibes aren’t great in New England following a blowout loss to the Jacksonville Jaguars, and there are major concerns surrounding the play of QB Drake Maye. He's looked nothing like the player who finished runner-up in MVP voting last season.

The mood is quite the opposite for Buffalo, who comes into the week undefeated after knocking off the Los Angeles Chargers 24-16 in Week 3. QB Josh Allen is the early favorite to win MVP, returning a 3.33x payout to win the award on PrizePicks.

Below, we’ll break down our Patriots vs. Bills prediction and picks for NFL Week 4, including the spread, over/under, and top player picks for PrizePicks.

Make your Patriots vs. Bills prediction and picks on PrizePicks now!

{{nfl_offer_banner="/style-system/ui-components-playbook"}}

Patriots vs. Bills Prediction, Spread, Over/Under – Sunday, October 4

There’s been a lot of discourse surrounding the struggles of Maye, who’s thrown just 1 TD through three weeks and already has 6 INTs. He threw 8 picks over 17 regular-season starts in 2025. 

According to RBSDM, Maye enters Week 4 ranked 28th among 34 qualified QBs in adjusted EPA/play (-0.034). Last season? He was first in the metric (0.322) among QBs with at least 100 plays.  

Many are chalking this up to Maye being a “schedule merchant” who only performed well last year due to the Pats’ easy slate. While there could be some truth to that, his steep drop in play might not be that simple. 

Maye popped up on the injury report with a right shoulder ailment this week, and while he practiced in full and downplayed the issue, it brings up memories of the shoulder injury he suffered in last season’s AFC Championship Game and affected his play in the Super Bowl.   

Chad Graff, The Athletic’s Patriots beat writer, suggested that Maye’s “confidence is shot.” Head coach Mike Vrabel shot down a report that there’s a rift between him and his QB. Star WR A.J. Brown remains sidelined with an ankle injury.

Two of Maye’s favorite targets last season, WRs Stefon Diggs and Kayshon Boutte, are no longer with the team.

Whatever the case may be, it'll be very hard to trust this Patriots offense unless the signal-caller improves his play. The team is tied for last in points per game (12.0) and is 21st in yards per game (307.0).

On the bright side, the Patriots have been much stronger on the other side of the ball. Despite allowing 35 points to the Jaguars last week, New England’s defense has given upthe sixth-fewest PPG (17.0) and fifth-fewest YPG (278.3) while being 12th in EPA/play allowed (-0.050) and eighth in defensive DVOA, per FTN.          

The defense will likely have to be at its best to slow down Allen and company.

While Allen is coming off a shaky 2-INT performance against the Chargers, he ranks fourth in adjusted EPA/play (0.356) and has helped the Bills rank first in PPG (33.7) and fourth in YPG (401.7).

Buffalo’s defense has been the far weaker unit, ranking 25th in EPA/play (0.091) and 27th in success rate (48.4%). The Bills have given up the 11th-most PPG (26.0) and eighth-most YPG (361.3).

While those numbers leave a lot to be desired, if there’s one bit of good news for that Bills’ defense, it’s that it's sixth in sacks (9). That may be crucial on Sunday against a QB who’s struggled mightily with turnovers.

Patriots vs. Bills Spread, Over/Under – Sunday, October 4

The Bills enter Sunday’s game as 6.5-point home favorites against the Patriots, returning a 1.29x payout on PrizePicks if they win outright.

Make your Patriots vs. Bills prediction on the spread on PrizePicks!

PrizePicks data is live at the time of writing and is subject to change. 

Patriots vs. Bills Prediction on Spread – 10/4/26

Here are the key stats and trends behind our Patriots vs. Bills prediction on the spread for Sunday, October 4.

• The Patriots’ offense is 28th in EPA/play (-0.130) and 27th in success rate (40.1%). The Bills rank second (0.228) and fifth (50.3%), respectively, in those metrics. 
• In New England’s disastrous performance against the Jaguars, it produced -0.324 dropback EPA/play. Only the Philadelphia Eagles had a worse mark in their MNF loss to the Chicago Bears.
• The Patriots’ attack also ranks dead last in offensive DVOA.
• According to PFF, Maye has the highest turnover-worthy play rate (8.6%) among all QBs with at least 30 dropbacks.
• Buffalo’s high sack total is backed by the team ranking sixth in pressure rate (39.8%), per Sharp Football Analysis. PFF also grades the defense as having the NFL’s second-best pass rush. 
• Maye has the league’s fourth-highest sack rate (10.1%), and his offensive line has ceded the seventh-highest pressure rate (42.5%).
• Despite the Patriots generally performing well on defense, they’re 28th in rush EPA/play allowed (0.003). They’re about to face a Bills offense that’s first in rush EPA/play (0.073). 
• New England will be without CB Christian Gonzalez and DT Christian Barmore, which is a sizable blow to the defense this weekend. 

Make your Patriots vs. Bills picks on PrizePicks for Sunday’s NFL game.

Patriots vs. Bills Picks, Player Stats for PrizePicks: 10/4/26

Here are the top Patriots vs. Bills picks to target on Sunday, October 4. Today’s NFL picks for PrizePicks include James Cook and DJ Moore.

Bills RB James Cook vs. Patriots: 85.5 Rush Yards

• Cook has averaged 19.3 carries and 115.3 rushing yards per game. Over the past two weeks, he’s rushed for 135 and 154 yards. The Buffalo RB leads the sport in yards per carry at 6.0.
• Per PlayerProfiler, Cook is first in both explosiveness rating (134.9) and breakaway runs (6). He’s also benefited from the best run block rating (116.0).
• With the Bills coming in as nearly TD favorites at home, Cook could benefit from a positive game script if the offense can get out to an early lead.
• While Allen can take some rushing opportunities away from Cook, he otherwise has virtually no competition for carries as a true workhorse back. Buffalo’s backup RBs have accounted for just 2 rushes all season.
• In addition to the Pats’ D ranking 28th in rush/EPA play allowed, it's last in rush stuff rate (8.1%).

Add James Cook + Bills to cover the spread to your PrizePicks lineup now.

{{nfl_offer_banner="/style-system/ui-components-playbook"}}

Bills WR DJ Moore vs. Patriots: 49.5 Rec Yards

• Moore was limited in practice this week but is off the injury report. He could benefit from the absence of Gonzalez, the Patriots’ top cornerback.
• Moore has averaged 9.0 targets, 5.5 receptions, and 83.5 yards across his two healthy games. Despite missing most of Week 2, he still leads the team in targets (18).   
• The wideout is averaging 2.88 yards per route run. That’s the eighth-best mark among WRs with at least 10 targets.
• Per ESPN, the Bills’ offensive line is first in pass block win rate, which could help give Allen time to get the ball to his top wideout.  

Add DJ Moore + Bills to cover the spread to your PrizePicks lineup now.

Make Patriots vs. Bills Picks on PrizePicks

The New England Patriots badly need to turn things around before their season goes down the drain. Can they find a way to rebound despite being a road underdog against the Buffalo Bills? 

Don't wait until kickoff — make your Patriots vs. Bills picks on PrizePicks now for Week 4 and earn real money if you're right.

Pick players, predict More or Less on their stats, and cash in if you’re right. With Team Picks, you can make predictions on NFL game winners, spreads, and over/unders, now available in 36 states.

Stay locked in on Playbook for daily NFL news, picks, analysis, and more all the way through Super Bowl LXI.