San Francisco 49ers vs Buffalo Bills Prediction, Odds and Picks for Sunday, 12/01/24

This is a line that I could see being flipped by the time we get to late November, so for our 49ers vs Bills prediction, why not take a shot with one of the best home teams in football? Prior to this Sunday Night Football matchup in Week 13, the 49ers will have played a 5-game stretch consisting of the Chiefs, Cowboys, Buccaneers, Seahawks and Packers. Not only were 4 of those 5 teams in the playoffs last season, but the 49ers will have just played the Packers at Lambeau Field in a massive revenge spot for Green Bay the week prior to this contest. On the other hand, the Bills will be coming off a much-needed bye week after completing a pivotal 8-game stretch of their schedule.

There’s an argument to be made that the 49ers are overvalued in the market heading into this season, so this number could easily be Bills -2.5 by the time we hit kickoff. Yes, Buffalo can be frustrating in close games against lesser competition, but Josh Allen and company have typically risen to the occasion in these home spots (see: last season vs Miami & Dallas), so it’s hard not to back the Bills as home underdogs in this one for our 49ers vs Bills best bet.

49ers vs Bills prediction: Bills ML (+110) available at time of publishing.

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