The Week 5 Sunday Night Football matchup features the New England Patriots heading to Orchard Park for a meeting with the undefeated, AFC East-leading Buffalo Bills. We’ll be diving into all of the primetime games this season, and this one isn’t any different. With that in mind, keep reading for betting odds, picks and player props for this exciting showdown. Also, make sure you head over to our Week 5 NFL Betting Hub for a look at all of our NFL betting content.

MORE: Head to the Pro Picks page for best bets from all of our VSiN hosts and analysts!

How To Watch Patriots vs. Bills

When: Sunday, October 5 at 8:20 pm ET

Where: Highmark Stadium in Orchard Park, New York

Channel: NBC

Patriots vs. Bills Odds

Odds from DraftKings Sportsbook as of Saturday, October 4. Look around for the best prices!

Moneyline: Bills -425, Patriots +330

Spread: Bills -8.5 (-105), Patriots +8.5 (-115)

Total: Over 49.5 (-115), Under 49.5 (-105)

Patriots vs. Bills Analysis

The Bills went down 40-25 in their Week 1 game against the Ravens, and they’ve been the best team in football since that very moment. Buffalo came back to win that game 41-40, and the team comes into this one after having won three straight games by double digits. That’s part of the reason why the Bills are getting nearly 75% of the tickets at Circa Sports, according to our VSiN betting splits. However, the Patriots have gone from +8.5 to +7.5 there, suggesting there’s some important money on the road team. New England was also +10 at DraftKings Sportsbook when lookahead lines became available for Week 5, but the team is down to +8.5 now.

Grabbing the points in this game does feel like the right move. The last four meetings between these teams were decided by one score. Also, since 2021, home teams facing division opponents after a non-conference game are 46-84 against the spread. Backing the road team in that situation would put you up 33.4 units, and that situation was 2-0 in the 2025 NFL season heading into Week 5.

The Patriots have also gotten themselves going lately. This defense still isn’t up to Mike Vrabel’s standards, ranking 23rd in the league in EPA per play allowed (0.051). However, this offense has been something else. While Buffalo is first in the NFL in EPA per play (0.243), New England is up to No. 9 in the league (0.082). Also, since Week 1, the Bills have an EPA per play of 0.218 while the Pats have an EPA per play of 0.134.

The New England passing game is what’s cooking. Since Week 1, the Patriots are first in the NFL in Dropback EPA per play (0.433). Drake Maye is also first in the NFL in completion percentage (74.0%) right now, plus he has thrown for 988 yards with seven touchdowns while adding another two scores on the ground. The Bills defense has been good against the pass this year. But how much of that is opponent-based? Lamar Jackson shredded this secondary in Week 1, then Buffalo righted the ship against Justin Fields, Tua Tagovailoa, and Spencer Rattler. Big deal.

I’m not sure Maye will be able to actually go into Buffalo and come away with a victory, but it’s going to be hard for the Bills to cover 8.5 if the Pats are consistently moving the ball. And there’s really no reason New England can’t do that. Not only has Maye been putting it on his receivers, but he’s constantly throwing to open ones. Josh McDaniels has been consistently scheming his guys open, which is why Maye is lighting opponents up despite having a weak receiving corps. And McDaniels has seen this defense a million times, so he should be able to bring a good game plan to the table.

There’s also a good chance the New England running game is a big factor here. The Bills are just 24th in the NFL in Rush EPA per play allowed (-0.020), and Buffalo has some talented backs. If those rushers can just hang on to the football, we could see some big chunks picked up on the ground — and some short-yardage situations for Maye.

The Over could also be worth a look in this game. While it’s definitely on the higher side, these are two of the best passing games in the league. And realistically, even if you’re like me and you like the Patriots, it’d be foolish to think that the Bills won’t get going in this one. Josh Allen is the best quarterback in the league, James Cook has played like one of the best running backs in the league, and Joe Brady is going to dial up some good stuff against this shaky New England secondary. The Over is also 15-9-2 in the home games the Bills have played with totals of 49.5 or higher under McDermott. So, when shootouts are expected, shootouts are generally what they get.

Patriots vs. Bills Player Props

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Hunter Henry Anytime TD Scorer (+260 – 0.5 units)

There’s a clear connection between Maye and Hunter Henry. The tight end had a career year in 2024, catching 66 passes for 674 yards. And he did a good amount of that work with the talented young quarterback under center. This year, Henry is on pace to be even better. While he’ll likely slow down at some point, Henry is on pace to catch 64 passes for 867 yards and 13 scores.

I was tempted by going Over on Henry’s yards or receptions, as this should be a game in which Maye will need to throw a lot to keep pace with Allen and the Bills offense. However, Buffalo has done a good job of keeping tight ends in check this year. Sure, the Bills haven’t faced many good ones, but Mark Andrews only had one catch for five yards against them in Week 1. So, when looking for a way to back Henry, the right move could be taking the 30-year-old to find the end zone.

Henry has three touchdowns over the last two weeks, and he leads all tight ends in red zone targets (6) this year. When the Pats get down by the goal line, Maye looks Hunter’s way. There’s value in that at +260 odds, even if you’re just sprinkling it.

Patriots vs. Bills Pick

With the way Maye is spinning it right now, it’s hard to imagine New England losing this game by more than a touchdown. Vrabel’s personality also appears to be rubbing off on his team, which has now won and covered in two of the last three — and probably would have won three in a row if not for a billion Rhamondre Stevenson fumbles.

Bet: Patriots +8.5 (-112 – 1.5 units) & Henry Anytime TD (+260 – 0.5 units)

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