The Buffalo Bills will host the New England Patriots on Sunday Night Football in Week 5 of the NFL season. Buffalo is off to an undefeated start and is the betting favorite to win this year’s Super Bowl. They will try to get a key division win over a Patriots team that is playing much-improved football compared to a season ago. Here, I break down this AFC East rivalry game and bring you my Patriots vs Bills prediction.
Our Patriots vs Bills Pick
- Pick: Buffalo Bills –7.5
- Confidence: ★★★★☆
Game Snapshot
- Matchup: New England Patriots @ Buffalo Bills
- Date & Time: Sunday, October 5, 2025, 8:20 p.m. ET
- Venue: Highmark Stadium, Orchard Park, NY
- Broadcast: NBC
Patriots vs Bills Odds
| Spread | Moneyline | Total |
|---|---|---|
| Bills −7.5 | Patriots +320 | Bills −425 | 49.5 |
Key Storylines
Buffalo enters this game off a 31–19 win over the Saints in Week 4, with Josh Allen tossing two touchdowns and adding a rushing touchdown. Running back James Cook racked up over 100 yards on the ground in the win. The Bills are the only undefeated AFC team left after Week 4. Their offense is humming and their defense has allowed 16.7 points per game after a rough opener against the Baltimore Ravens.
Week 4 was an encouraging sign for the New England Patriots. The Patriots trounced Carolina 42–13. Rookie QB Drake Maye was sharp, going 14-of-17 with 203 yards, two passing touchdowns, and a rushing touchdown. Their special teams made a splash via Marcus Jones’ 167 punt return yards, including an 87-yard touchdown.
New England is trying to build an identity under head coach Mike Vrabel and offense coordinator Josh McDaniels. This will be their toughest test yet, on the road against an undefeated division rival that is playing at a high level.
Quarterback Play
Josh Allen looks like a threat to win a second straight NFL MVp award. Though he hasn’t been forced into heroics every week, he’s taken what the defense has given him and avoided making mistakes. Allen has just one interception through four games and that is a great sign for the Bills early in the year.
Drake Maye has looked very promising early in the season for the Patriots. He is very close to Allen in most major passing stats early on. But against a Bills defense with speed and depth, Maye will be tested more than ever.
Betting Trends
- Both teams are 2-2 against the spread so far this season.
- Buffalo is 3-1 to the over through their first four games.
- New England is 2-2 on over/unders going into Week 5.
Patriots vs Bills Model Projection
- Score Projection: Buffalo 30 – New England 20
- Win Probability: Buffalo 68%, New England 32%
Final Thoughts
The Buffalo Bills have looked miles better than anyone in the AFC through the first four weeks of the season. Buffalo is operating at a high level on both sides of the ball and they have won three straight games by double-digits. I expect them to win a fourth straight game by double-digits here, as the Bills should cover the spread at home on Sunday Night Football.
Affiliate Disclosure
ATS.io features affiliate links to licensed online casinos, sportsbooks, and gambling platforms. That means if you click on them and end up signing up or making a deposit, we might earn a commission at no extra cost to you. We only work with licensed and reputable online casinos, social casinos and sportsbooks. Our content whether it’s reviews, guides, or betting tips is written with the goal of being honest, helpful, and based on real experience. While we do earn through affiliate partnerships, it doesn’t affect our recommendations. If a site isn’t safe or doesn’t meet our standards, we won’t promote it. Simple as that. We also take responsible gambling seriously. We encourage all our readers to gamble safely, set limits, and know when to take a break. Have questions? Feel free to reach out. We’re always happy to chat.
- SCCG Management. The Gambling Industry’s Global Connector. Access Here.
- Source: https://ats.io/nfl/new-england-patriots-vs-buffalo-bills-prediction-10-5-2025/469241/