49ers-Bills Betting Angles

With a steady stream of good injury/COVID news for the 49ers this week, don't be surprised if this game opens at a pick' em.
Publish date:

Point Spread: 49ers +1.5

Total (Over/Under): 48

Line movement

Buffalo opened as a 3-point favorite Sunday night after the 49ers surprised many, upsetting the Rams 23-20. The line dropped to Buffalo -2.5 Monday morning, briefly popped back to -3 at many shops, and since then has dropped down to -1.5. Some books (Bet MGM, Draft Kings, Westgate) have Buffalo -1 so shop wisely. Betters don't seem bothered by the Niner home game being moved to a neutral location (Arizona). With a steady stream of good injury/COVID news for the 49ers this week, don't be surprised if this game opens at a pick' em.

The over/under has remained consistently at 48, with a very brief stint at 48.5 Monday morning. Assuming there are no weather concerns, Monday Night Football games typically see totals rise right before kickoff. In other words, if you're going to bet the game over, bet it now. If you're going to be the game under, wait until right before kickoff for a better number.


The weather in Glendale, AZ is projected to be in the high 60s around kickoff with 0% chance of precipitation and winds around 8 MPH. Wind, not precipitation, is the key indicator to look for as a potential impact to points being scored so you can bet this game without worrying about weather.


Buffalo is 7-3-1 to the over this season. The 49ers are only 1-4 ATS at home this season, so perhaps having a "home" game in Arizona might not hurt as much as people think. When you have no fans in your stadium, home field advantage is mostly negated anyways.

These teams haven't played since Buffalo destroyed the 49ers 45-16 in 2016, thanks to LeSean McCoy's 140-yard, 3 TD performance. San Francisco is 6-6 lifetime vs. Buffalo with the 49ers winning 3-of-5 since 2001.

Injury front

San Francisco is getting healthy at the right time. Raheem Mostert, Deebo Samuel and Richard Sherman all returned last week and had big games. This week, D.J. Jones, Brandon Aiyuk and special-teams ace Mark Nzeocha are expected to return.

Of those, Aiyuk should provide the biggest boost as the 49ers will have him and Samuel on the field together for the first time since October 25th.

The Bills injury situation is trending in the opposite direction, with left guard Cody Ford and deep threat John Brown landing on IR recently.

The 49ers' secondary is playing extremely well and not having Brown allows them to key on Stefon Diggs and Cole Beasley. Brown and Diggs on the outside with Beasley in the slot would have threatened the 49ers who will be without both of their top two nickel corner backs.

In Diggs' past two games against the 49ers as a member of the Vikings, he posted five catches for 100 yards and two touchdowns. However, both touchdowns (41 yards and 22 yards) were in 1-on-1 coverage against Ahkello Witherspoon who, barring injury, should spend most of the day on the bench.

Josh Allen suffered a knee injury against the Chargers and though he's expected to play, a knee injury to a mobile quarterback is noteworthy.

Best bets

49ers +1.5

49ers ML (EV)

The 49ers are closer to a playoff spot than those outside the organization realize. They'll be playing with intensity and will be eager to get the taste out of their mouth from embarrassing prime-time losses to the Eagles and Packers. I love the match up and I love when a short home underdog has line movement in their favor earlier in the week.

Last week's best bet

Last week I suggested grabbing the 49ers at +7, as predicted the line dropped, giving us good closing line value, and the 49ers didn't let us down, covering easily with a 23-20 win.