The Buffalo Bills have had two weeks to enjoy their win over Patrick Mahomes in Week 11, but that has also been more time to reset and get ready for the San Francisco 49ers, who are in a bad spot health-wise Sunday night.
With almost everything working against San Francisco, my 49ers vs. Bills predictions don't expect the visitors to put together much offense on December 1. Kickoff is scheduled for 8:20 p.m. at Highmark Stadium in Orchard Park, with the game airing on NBC.
Read more in my NFL picks below.
49ers vs Bills SNF prediction
Who will win 49ers vs Bills?
Let’s keep this simple. Sunday night is a game between the MVP-betting favorite quarterback Josh Allen, who is coming off extra rest and having the healthiest offense he’s had all year.
They’ll face a cross-country traveling San Francisco 49ers team that might still be without its starting quarterback, is decimated with injuries on both sides of the ball, and might realize it doesn't have the personnel to get to the playoffs this year.
Now add possible severe weather, which includes freezing temperatures, possible snow, and winds exceeding 20 mph. This is a bad game for the visiting offense
This spread is very vulnerable at -7 for the home side, who is 5-0 SU at home (3-2 ATS) and has scored 30+ points in each game. The Brock Purdy news will sway this number to either side of this flat spread, but I’ll gladly take the Bills off the bye, getting healthy, and with this projected weather as a touchdown fave at close to even money.
This is not anywhere near the San Francisco team that bettors are used to as even Christian McCaffrey seems to be a shell of his 2023-24 self. It's the Bills all day Sunday night.
49ers vs. Bills score prediction: Bills 27, 49ers 14
My best bet
Pick: 49ers team total Under 19.5 (-135 at bet365)
My analysis
The Buffalo Bills might have been in a letdown spot after a massive and convincing win over the Chiefs, but a week off was likely the perfect thing for them to regroup, refocus, and get healthy.
The Bills took down the undefeated Chiefs without linebacker Matt Milano, receivers Keon Coleman and Amari Cooper, tight end Dalton Kincaid, and tackle Spencer Brown. Now, they might not get all of these names back, but Kincaid was the only DNP player on Wednesday.
This is in sharp contrast to a San Francisco 49ers team in freefall, crossing the country after a humiliating defeat to the Packers last Sunday.
In San Francisco’s 38-10 loss in Lambeau, it was without quarterback Brock Purdy, Tackle Trent Williams, defensive back Charvarious Ward, and EDGE Nick Bosa.
It's not going to be easy to get these guys healthy, as Bosa and Williams were DNP at practice on Wednesday, and Purdy was limited but did not throw a football. It also has come out linebacker Fred Warner is playing with a broken ankle.
Now add in the most important factor facing this water-downed San Francisco offense — the weather.
The words severe weather are getting thrown around on Sunday night in Orchard Park, and that means freezing temperatures, 20+ mph winds, and possible snow. This will be a big home-field advantage for the Bills, especially if Purdy can’t get healthy and Brandon Allen is back under center.
In the 49ers’ seven second-half possessions in Green Bay last week, Allen led this offense to a field goal, a punt, and five turnovers (an interception, two fumbles, and two failed fourth-down conversions). The Bills are a great turnover defense and could have their best game under the prime-time lights Sunday night.
If the weather was better, I’d be hitting the Bills’ team total Over 27.5, but I think this weather, combined with the Purdy/Allen situation, is a potential disaster for a failing San Francisco offense.
Purdy at less than 100% with a bad shoulder or backup Allen, I don't care. This San Francisco offense is going to struggle to get 20 points.
The 49ers team total Under 19.5 points is only getting to get shorter as Sunday approaches. There is not much I like on either side of the football for the visitors.
49ers vs Bills SNF same-game parlay
49ers team total Under 19.5
Josh Allen anytime touchdown
Bills Over 1.5 rushing touchdowns
There are next to zero player props available due to the number of injuries on both sides. Add in some severe weather conditions, and this game could be a nightmare for player props anyway.
This looks like a perfect time for the Bills to dominate the TOP with a healthy running game that features three rested backs. Allen will continue to do what he needs to do for the No. 1 seed in the AFC, and that means rushing in his own TD in bad conditions, which is on brand for December Allen.
I'm not sure the multiplier for the rushing TD total is correct, but I'll take it.
Learn how to bet a same-game parlay with these helpful tips and strategies.
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49ers vs Bills odds
49ers vs Bills live odds
49ers vs Bills opening odds
- Spread: San Francisco +3 | Buffalo -3
- Moneyline: San Francisco +145 | Buffalo -170
- Over/Under: Over 47.5 | Under 47.5
Odds courtesy of bet365
49ers vs Bills spread and Over/Under analysis
- The Bills were 2-point home favorites on the opening lines, were -3 at bet365 on November 19, and then re-opened as a 4-point favorite Sunday night after the 49ers' loss to Green Bay. They were then bet up to -7 by late Sunday night.
- The total should take a hit to the Under once the public alarm of severe weather is alerted. This opened at 47.5 and was sitting at 44.5 as of Tuesday. I think there is still some room for this to fall if 20+ mph winds remain and the Purdy shoulder news doesn't improve.
49ers vs Bills betting trend to know
The Buffalo Bills have hit the 2Q Game Total Over in 14 of their last 18 games (+10.60 Units / 50% ROI). Find more NFL betting trends for 49ers vs. Bills.
How to watch 49ers vs Bills game info
| Location: | Highmark Stadium, Orchard Park, NY |
| Date: | Sunday, 12-1, 2024 |
| Kickoff: | 8:20 p.m. ET |
| TV: | NBC |
49ers vs Bills latest injuries
49ers vs Bills weather
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