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Buffalo Bills vs San Francisco 49ers Predictions, Odds & Picks

Written by: Mike Lukas
Updated October 14, 2022
12 min read
Bills Vs 49ers 2020
  • The Bills are 8-3 now and in charge of the AFC East, but only by a game
  • The banged-up 49ers do not seem capable of any kind of decent run for the postseason
  • These teams last played in 2016, when the Bills beat the 49ers, final score 45-16

Bills vs 49ers Odds

Team Point Spread Odds
Buffalo Bills -1
San Francisco 49ers +1


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Bills vs 49ers Predictions and Picks

Compared to San Francisco, at this point in the season, the Bills are the more effective and healthier team and should be able to beat the 49ers and cover this narrow spread.


Bills -1 (-105)

How to Watch Bills vs 49ers

Bills vs 49ers Information
What Buffalo Bills vs San Francisco 49ers
Where Levi’s Stadium in Santa Clara, CA
When Monday, December 7, 2020; 8:15 PM ET
How to watch ESPN / ABC

A productive season by Buffalo Bills young QB Josh Allen has them at 8-3 now and in charge of the AFC East, but only by a game over the Dolphins, so a Week 13 victory over these bruised up Niners would help keep them ahead of those Phins and in a good position for the upcoming playoffs.

The 5-6 San Francisco 49ers are last in the NFC West and now have seventeen players out plus they have no home facility in Santa Clara thanks to the new COVID restrictions that are in place, so making any kind of a run for the postseason seems impossible, especially facing these powerful Bills so late in the season.

These two cross-conference rivals have met each other 12 other times, with the San Francisco 49ers winning 6 of those games and the Buffalo Bills also winning 6 of the games.

Can Bills QB Josh Allen Continue to Play at This High a Level?

This is QB Josh Allen’s third National Football League season, all with the Bills, the team that drafted him in the first round (7th overall) and have expected big things from him as the starter since his rookie season, and the former Wyoming Cowboy has not disappointed.

This year Allen has the Bills at 8-3 and in charge of the AFC East for the first time in forever, and he has completed almost 69 percent of his passes this year and has completed 267 of them for 3,028 yards and 22 touchdowns with 8 interceptions along the way.

Allen threw 2 picks in Week 10 against the Cardinals and that led to one of their three losses, so the key to getting a win over these nasty Niners could be to take excellent care of the ball and be better prepared to throw it away and live to fight another down.

Can the 49ers Roster Get Healthy This Season?

Star DE Nick Bosa (knee – ACL) is out, along with DE Dee Ford (neck), QB Jimmy Garoppolo (ankle), TE George Kittle (foot) and WR Jalen Hurd (knee-ACL), and the list of 49ers big-name playmakers who are gone for the season just keeps getting bigger as more games are played.

So, the question becomes whether the team can get healthy enough to compete for the rest of this season and vie for one of the three NFC Wild Card spots that are up for grabs this season.

Currently, the Niners are 10th in line for the seven total NFC playoff spots, and ahead of them are two other 5-6 teams (Vikings and Bears), so if the team can rally again as they did against the Rams in Week 12, they could still have a slim shot at playing football in January.

Editor’s Picks

Bills Key Player: (DT) Ed Oliver

In his second NFL season, Bills defensive tackle Ed Oliver was a first-round pick and the 6’ 1” 287-pound beast has not let his pro team down, becoming a huge part of the Buffalo pass rush that has opposing QBs shaking in their cleats.

Oliver has solid numbers in 2020, especially for such a young player, so far with 2 sacks, 4 quarterback hits, 2 passes defended, a forced fumble, and 24 total tackles, with 3 of those being for a loss.

For the Bills to win in Week 13 over this run-heavy 49ers team – they average 112 yards on the ground per game – Oliver and his front line including DT Harrison Phillips, DEs Mario Addison and Jerry Hughes must have a big game going after opposing QB Nick Mullens.

49ers Key Player: (QB) Nick Mullens

The San Francisco backup QB is Nick Mullens, and since starter Jimmy Garoppolo is out for the season with an ankle injury, it becomes his job to pull this 49ers offense together and figure out how to win some games.

Right now San Fran boasts the 14th most productive team on that side of the ball, averaging 363 total offensive yards and almost 24 points per game, numbers that aren’t mind-blowing but do not seem bad enough to cause a losing 5-6 record.

Mullens has to step up and be more careful with the ball (he has 7 interceptions already with just 6 TD passes) although he is completing a decent number of the throws he attempts (67.5%), so he has the skills, now if only he can get some healthy San Fran playmakers onto the field with him.

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Mike Lukas

1204 Articles

Mike Lukas is a retired standup comedian turned freelance writer now living in Dallas, Texas, originally from Cleveland, Ohio. His love for the game of football and all things Cleveland Browns turned Mike into a pro blogger years ago. Now Mike enjoys writing about all thirty-two NFL teams, hoping to help football gamblers gain a slight edge in their pursuit of the perfect wager. Email: [email protected]

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