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The San Francisco 49ers and Buffalo Bills was a Sunday Night Football game that looked promising when the schedule came out before the season. However, many injuries in both locker rooms have taken away some of the drama. The 49ers' poor record also hasn't done much to get us excited for this game, and the Bills could put a dagger into their playoff chances with a win. The 49ers wouldn't be close to a playoff spot in most divisions, but they are one game out of first thanks to the Seattle Seahawks and Arizona Cardinals' 6-5 record. It is time to continue our NFL odds series with a 49ers-Bills prediction and pick.
49ers-Bills Last Game – Matchup History
The 49ers and Bills could be two of the NFL's most historic and well-known franchises, but they haven't played as often as you think. The teams' schedules don't match up too frequently, and the last time they faced off was in 2020, with the Bills winning 34-24. Josh Allen was a star when he played the 49ers in 2020, throwing for 375 yards and four touchdowns. Dawson Knox is the only touchdown pass-catcher remaining on the Bills' roster from that game.
Overall Series: Bills 7-6
Here are the 49ers-Bills NFL odds, courtesy of FanDuel.
NFL Odds: 49ers-Bills Odds
San Francisco 49ers: +7 (-115)
Moneyline: +255
Buffalo Bills: -7 (-105)
Moneyline: -315
Over: 44.5 (-110)
Under: 44.5 (-110)
How to Watch 49ers vs. Bills
Time: 8:20 PM ET/5:20 PM PT
TV: NBC
Stream: fuboTV (Free Trial)
Why The 49ers Could Cover The Spread/Win
Time is running out for the 49ers, and Kyle Shanahan has to find a way to start stringing some wins together despite their injury issues. San Francisco won three of four games entering their Week 11 matchup with the Seahawks, but their offense hasn't looked good. The 49ers scored just 17 points against the Seahawks, then followed it up with 10 points against the Green Bay Packers.
Why The Bills Could Cover The Spread/Win
The 49ers' injury report will tell the tale of their chances in this game. At this point, there isn't much reason to believe in San Francisco, and it'd be an excellent chance to jump on this number before any players go from questionable to out and boost the number. The injury report currently has Trent Williams, Brock Purdy, and Nick Bosa, which would be a disaster if they didn't suit up for this game. The Bills' injury report doesn't look good either, especially with their wide receiver room, as Keon Coleman, Curtis Samuel, Amari Cooper, and Mack Hollins are all on the initial report. However, it seems like they all have a better chance of playing.
The Bills have been on an unbelievable run, culminating in their victory over the Kansas City Chiefs in Week 11 to ruin the undefeated season. Buffalo had a bye in Week 12, which means they should be coming at the 49ers rested and relatively healthy. The Bills have won six games in a row and covered all but one, a division matchup with the Miami Dolphins.
Final 49ers-Bills Prediction & Pick
As previously mentioned, this number will increase if the 49ers announce that any of their stars are confirmed out. Even if some of those players play, the Bills to win this game by at least a touchdown seems like a great bet. Take the Bills to keep it rolling and dent the 49ers' Super Bowl dreams.
Final 49ers-Bills Prediction & Pick: Bills -7 (-105)
