Bills vs. 49ers odds, prediction, spread, start time: Sunday Night Football picks from NFL model on 22-8 run

The Buffalo Bills (9-2) and the San Francisco 49ers (5-6) are set to square off on Sunday Night Football. The Bills can clinch the AFC East with a victory and win their fifth-straight division title. Buffalo leads the all-time series 7-6, including two straight wins over San Francisco. The 49ers are currently 11th in the NFC playoff picture. The 49ers vs. Bills weather forecast is calling for two to three feet of snow ahead of Sunday Night Football. Quarterback Brock Purdy (shoulder) is questionable for the 49ers after sitting out last week but he’s expected to play. 

Kickoff from Highmark Stadium in Buffalo is set for 8:20 p.m. ET. Buffalo is a 6.5-point favorite in the latest 49ers vs. Bills odds from the SportsLine Consensus, while the over/under for total points scored is 44.5. The Bills are -285 money line favorites (risk $285 to win $100), while the 49ers are +231 underdogs (risk $100 to win $231). Before locking in any 49ers vs. Bills picks, make sure to check out the NFL predictions and betting advice from the SportsLine Projection Model.

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on top-rated NFL picks since its inception. The model enters Week 13 of the 2024 NFL season on an incredible 22-8 betting hot streak on top-rated NFL picks this year. Longer term, it is on a 202-136 roll on top-rated NFL picks that dates back to the 2017 season and a 56-29 roll on top-rated NFL picks since Week 7 of 2022.

The model also ranked in the top 10 on NFLPickWatch four of the past six years on straight-up NFL picks and beat more than 94% of CBS Sports Football Pick’em players four times during that span. Anyone following at sportsbooks and on betting apps has seen strong returns.

Now, the model has simulated 49ers vs. Bills 10,000 times and just revealed its coveted NFL picks and NFL betting predictions. You can head to SportsLine now to see the model’s picks. Here are several NFL odds and NFL betting lines for 49ers vs. Bills:

• Bills vs. 49ers spread: Buffalo -6.5
• Bills vs. 49ers over/under: 44.5 points
• Bills vs. 49ers money line: Buffalo -285, San Francisco +231
• SF: 49ers are 4-7 against the spread this season 
• BUF: Bills are 7-4 against the spread this season
• Bills vs. 49ers picks: See picks at SportsLine
• Bills vs. 49ers streaming: FuboTV (Try for free)

Why the Bills can cover

Running back James Cook is a terrific weapon on the offensive side of the ball. Cook is agile with great vision as a ball carrier. In 2024, the Georgia product is tied for fourth in the league in rushing touchdowns (10) to go along with 596 rushing yards. He has five games this season with 50-plus rushing yards.

Quarterback Josh Allen continues to play at an elite level. He will push the ball downfield but also runs with power and force. This season, he’s 14th in passing yards (2,543), tied for sixth in passing touchdowns (18), and third in QBR (73.2). Allen has also rushed for 316 rushing yards with five rushing scores. In his last contest, Allen had 262 passing yards, 55 rushing yards, and two total touchdowns. See who to back at SportsLine.

Why the 49ers can cover

Running back Christian McCaffery returned to the field in Week 10 and provided his team with a reliable weapon. McCaffery has strong hands as a pass-catcher with the ability to be a dynamic ball carrier. Over three seasons with the 49ers, the 28-year-old has 2,354 rushing yards, 1,160 receiving yards, and 31 total touchdowns. He had 12 games with 100-plus scrimmage yards last season.

Tight end George Kittle is another dynamic weapon in the passing attack. Kittle can win on all three levels and is a menace after the catch. He’s third in the NFL in receiving touchdowns (eight) with 49 receptions for 642 yards. The Iowa product has six straight games with at least 50 receiving yards. In his last outing, Kittle had six catches for 82 yards and a score. See who to back at SportsLine.

How to make 49ers vs. Bills picks

SportsLine’s model is leaning Over the total, projecting the teams to combine for 47 points. The model also says one side of the spread cashes in more than 50% of simulations. You can head to SportsLine to see the model’s picks. 

So who wins 49ers vs. Bills on Sunday Night Football, and which side of the spread cashes over 50% of the time? Visit SportsLine now to see which side of the 49ers vs. Bills spread to back, all from the model that has returned well over $7,000 on top-rated NFL picks, and find out.