Tampa Bay Buccaneers vs Buffalo Bills Prediction, Odds and Picks for Sunday, 11/16/25

In a week full of compelling matchups, one of the most interesting games of the week comes in Buffalo, where the Bills are set to host the Buccaneers in a game that could go a long way to decide the fortunes of both teams in terms of playoff seeding in their respective conferences. Both teams are coming off pretty demoralizing losses, with the Bills dropping a game to the Dolphins as significant favorites a week ago, while the Bucs lost at home to a red-hot Patriots team, which marked the second defeat in the last 3 games for Tampa Bay. While this would ordinarily be a spot where I look to back the Bills at home — especially with Buffalo coming off a very poor performance in Miami — I can’t quite get there with this number given the matchup at hand and how the injury report looks for Sean McDermott’s side.

For starters, the Bills offense almost entirely centers around the ground game under offensive coordinator Joe Brady, and we just saw Miami be able to successfully bottle that up last week. When the Bills can’t get ahead of the chains early, it becomes a lot harder for Josh Allen and company to consistently convert in obvious passing situations on 3rd and long. The Buccaneers have a solid matchup edge in this game given that they have a top 3 rush defense in the league per success rate, while also sitting at 4th in rush DVOA on defense. Tampa Bay’s weakness is defending the pass, but given that the Bills might be without Dalton Kincaid — who has really become Allen’s top target in recent weeks — Buffalo might not have many answers against a Buccaneers defensive front that likes to blitz and can even get pressure on opposing quarterbacks by only rushing 4 guys. On the other side of the ball, the Bills defense is extremely banged up after suffering a few more losses a week ago. With that in mind, even though Baker Mayfield has come back down to earth in recent weeks, the Bucs should be able to move the ball enough to stay within one possession in this one. Points could be at a premium here, so I’ll take a shot on the ‘dog.

Buccaneers vs Bills prediction: Buccaneers +6 available at time of publishing. Playable to Bucs +5.5

You can bet on our Bucs vs Bills pick with BetMGM, where right now new users can activate your new BetMGM account ⚡ and receive $150 in bonus bets INSTANTLY if your first $10+ wager is a winner!