Patriots vs. Bills Final Score Prediction for NFL Week 5 (Can New England Hang Around?)

The Patriots are underdogs in Week 5, but can they cover?

The New England Patriots and quarterback Drake Maye are underdogs in Week 5. / Brian Fluharty-Imagn Images

The New England Patriots are back to .500 in the 2025 season, and they are looking to pull off a statement win as sizable underdogs against the undefeated Buffalo Bills in Week 5.

Josh Allen and the Bills have struggled to cover as a major favorite this season, going 1-2 against the spread, but they have yet to lose a game and have the No. 1 offense in the NFL based on EPA/Play.

Drake Maye and the Pats are coming off a huge win over the Carolina Panthers in Week 4, but can they turn in that strong of an offensive showing against a playoff-caliber opponent? 

Oddsmakers don’t seem to think so, setting the Pats as 7.5-point dogs on the road on Sunday night. 

All season long, the SI Betting team will be sharing our score predictions for each NFL game as a fun way to help bettors decide on their spread and total bets.

Using the latest odds and analysis for this Week 5 matchup, here’s my score prediction for the final game on Sunday. 

Patriots vs. Bills Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• Patriots +7.5 (-105)
• Bills -7.5 (-115)

Moneyline

• Patriots: +295
• Bills: -375

 

Total

• 49.5 (Over -108/Under -112)

After opening as 8.5-point favorites at home, the Bills are now favored by just 7.5 points against their AFC East rival. 

New England has picked up wins over Carolina and Miami this season, but it has yet to play well against a quality opponent. Now, it’s taking on an undefeated Buffalo team that has shown some cracks on the defensive side of the ball in back-to-back games. 

Patriots vs. Bills Final Score Prediction

Earlier this week, SI’s NFL betting insider Iain MacMillan shared why the Patriots are his upset pick of the week in his Road to 272 column: 

It's been a while since I've made this bold of an upset pick, but I see a lot of issues with this Bills team. Let's remember how weak their schedule has been since Week 1. Their last three games have come against the Jets, Dolphins, and Saints. Despite that, they rank only seventh in Net Yards per Play (+0.9), and their defense ranks 22nd in opponent EPA per play, 17th in opponent success rate, and 22nd in defensive DVOA. To have those numbers while playing three of the worst teams in the NFL is a real problem.

Meanwhile, Drake Maye has had a fantastic start to his sophomore season. He's sixth amongst starting quarterbacks in EPA+CPOE composite and adjusted EPA per play. Their defense has had some problems of its own, but they rank right around the same as the Bills in several categories.

This has all the makings of an offensive shootout, and if the Bills aren't careful, the Patriots have a chance of pulling off an AFC East upset. I'll take a shot on New England as a big-time underdog.

Both of these teams rank in the bottom half in the NFL in EPA/Play on defense, and while I’m not as bullish as MacMillan when it comes to the Pats pulling off an upset, I do think they can cover.

Buffalo has failed to cover some pretty big spreads over the last two weeks, and the Patriots have a good enough offense to keep this game within a touchdown – even on the road. 

Final Score Prediction: Bills 31, Patriots 26

---

Odds refresh periodically and are subject to change.

If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER.

Claim the latest DraftKings promo code offer today. Sign up and win your first $5 bet to get $200 in bonus bets instantly.