49ers vs. Bills Prediction, Odds, Spread, Injuries, Trends for NFL Week 13

Betting odds, pick and prediction for the San Francisco 49ers-Buffalo Bills matchup in Week 13 of the NFL season.

Can Buffalo Bills quarterback Josh Allen lead his team to a win as home favorites? / Gregory Fisher-Imagn Images

The Buffalo Bills are fresh off of their bye week heading into a Sunday Night Football matchup with the San Francisco 49ers, who are in serious danger of missing the playoffs this season.

After making the Super Bowl in the 2023 season, San Francisco is just 5-6 through 11 games and in last place in the NFC West. To make things worse, starting quarterback Brock Purdy missed the team’s last game against the Green Bay Packers with a shoulder injury, and San Fran was crushed, 38-10. 

Now, oddsmakers seem to think Purdy could miss Week 13, as they’ve set the 49ers as seven-point road dogs on Sunday – just the second time (last week was the first) they’ve been set as road underdogs in the 2024 season.

Josh Allen and the Bills are still firmly in the mix for the No. 1 seed in the AFC, and a win in Week 13 would be massive since this was supposed to be one of the tougher games on their schedule.

Here’s a breakdown of the odds, players to watch and my prediction for this primetime matchup. 

49ers vs. Bills Odds, Spread and Total

Odds via DraftKings Sportsbook.

Spread

• 49ers +7 (-115)
• Bills -7 (-105)

Moneyline

• 49ers: +245
• Bills: -305

Total

• 45 (Over -108/Under -112)

49ers vs. Bills How to Watch

• Date: Sunday, Dec. 1
• Time: 8:20 p.m. EST
• Venue: Highmark Stadium
• How to Watch (TV): NBC/Peacock
• 49ers record: 5-6
• Bills record: 9-2

49ers vs. Bills Betting Trends

• The 49ers are just 4-7 against the spread this season.
• The Bills are 7-4 against the spread this season.
• The Bills are 4-2-2 against the spread after a bye under Sean McDermott. 
• Buffalo is 3-2 against the spread as a home favorite this season.
• San Francisco is 0-1 against the spread as a road underdog this season.
• The OVER is 7-4 in Buffalo’s 11 games this season.
• The OVER is 6-5 in the 49ers’ 11 games this season. 

49ers vs. Bills Injury Reports

49ers Injury Report

• Trent Williams – questionable
• Charvarius Ward – questionable
• Kevin Givens – questionable
• Jacob Cowing – questionable
• Brock Purdy – questionable
• Nick Bosa – questionable 
• Aaron Banks – questionable
• Deommodore Lenoir – questionable
• Dominick Puni – questionable
• Jordan Elliott – questionable 
• Renardo Green – questionable
• Demetrius Flannigan-Fowles – questionable

Bills Injury Report

• Spencer Brown – questionable
• Keon Coleman – questionable
• Dalton Kincaid – questionable

49ers vs. Bills Key Players to Watch

San Francisco 49ers

Christian McCaffrey: If Purdy misses another game – or is limited – the 49ers will need to lean on the running game and Christian McCaffrey on Sunday night. Since returning from an Achilles injury, CMC has 43 carries for 149 yards (3.47 yards per carry) and 13 catches for 132 yards in three games. He has yet to find the end zone in the 2024 season. 

Buffalo Bills

Josh Allen: The MVP favorite entering Week 13, Allen has completed 64.0 percent of his passes this season for 2,543 yards, 18 touchdowns, and five interceptions. He’s also added 67 carries for 316 yards and five scores on the ground.  

49ers vs. Bills Prediction and Pick

Purdy’s status will likely alter the odds in this game, but as they stand on Tuesday, I don’t know how you could bet on San Francisco.

The 49ers scored just 10 points in Week 12, and they struggled on defense as well. Despite having a ton of talent on both sides of the ball – the 49ers rank ninth in EPA/Play on defense and fifth in EPA/Play on offense – San Fran can’t overcome losing Purdy and turning to Brandon Allen at quarterback.

Buffalo has been solid against the spread this season, and it ranks second in the NFL in offensive EPA/Play. I expect Allen to have a field day – similar to Jordan Love and the Packers in Week 12 – if San Fran can’t move the ball again. 

Pick: Bills -7 (-105)

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Odds refresh periodically and are subject to change.

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