NFL betting for Week 13's regularly-scheduled Monday Night Football game will see the AFC East-leading Buffalo Bills travel west to take on the San Francisco 49ers.
While technically a home game for San Fran, this contest will be played at a neutral site – State Farm Stadium in Glendale, AZ – after the 49ers were temporarily kicked out of their home due to Santa Clara County's tightened COVID-19 restrictions.
NFL odds saw the visiting Bills open as 2.5-point favorites, but early action has dropped the spread to just a single point, with the total at 48. Here are our best free NFL picks and predictions for the Buffalo Bills vs. San Francisco 49ers, with kickoff set for 8:15 p.m. ET on Monday, December 7.
Buffalo Bills at San Francisco 49ers Betting Preview
Weather
State Farm Stadium has a beautiful translucent Birdair fabric roof, but it could be open Monday night as it is expected to be around 69 degrees with a 6 mph wind and no rain. Be sure to monitor the gametime conditions of other Week 13 contests with our NFL weather info.
Key Injuries
Bills: Matt Milano LB (Questionable), John Brown WR (Out), Cody Ford T (Out), Josh Allen QB (Probable), T.J. Yeldon RB (Questionable), Mario Addison DE (Questionable).
49ers: Demetrius Flannigan-Fowles LB (Questionable), K'Waun Williams CB (Out), Tevin Coleman RB (Probable), Tom Compton G (Questionable), Ben Garland C (Out), Jimmy Garoppolo QB (Out), George Kittle TE (Out), JaMycal Hasty RB (Out), Dee Ford DE (Out), Weston Richburg C (Out), Nick Bosa DL (Out), Jonathan Cyprien S (Out).
Find our latest NFL injury reports.
Betting Trend to Know
San Francisco is 13-3 ATS in its last 16 Monday games, while the Bills are 0-3-1 ATS in their last four MNF appearances. Find more NFL betting trends for Bills vs. 49ers.
Against the Spread (ATS) Pick
Nobody would blame the Bills for getting flashbacks upon returning to State Farm Stadium, where three weeks ago they suffered a last-second loss to the Cardinals on what's now being dubbed as the "Hail Murray" play.
Buffalo still might be rattled from that game, however. The Bills had a bye week to get over that loss but returned to action last week when they hosted the Chargers—and delivered an uninspiring performance in a 27-17 win. Buffalo had three turnovers in the second half and QB Josh Allen mustered just 157 passing yards (and two turnovers of his own), against the 23rd-ranked DVOA defense, per Football Outsiders.
Buffalo will need to shake the cobwebs off against a 49ers squad that is coming off a 23-20 overtime win against the Rams, leaving them just one game out of a playoff spot in the tight NFC. No. 1 QB Jimmy Garoppolo and star TE George Kittle are still sidelined, but the offense does have top receiver Deebo Samuel back in action, along with RB Raheem Mostert and a defense that still has plenty of bite. The Niners held the Rams to just 308 total yards and forced four turnovers in their Week 12 win, and will look to cause more havoc for Allen, who had multiple turnovers in each of his last two games.
San Francisco desperately needs this win, while Buffalo is traveling across the country and could be peeking ahead to a Week 14 date with the currently-undefeated Pittsburgh Steelers. The Niners are also 1-4 SU and ATS at home this year...but since this "home" game isn't, well, at home, we can put more stock in their 4-2 SU/ATS record away from Levi's Stadium.
PREDICTION: San Francisco +1 (-110)
Over/Under Pick
Last week's result snapped a three-game Over streak for Buffalo, while San Fran has seen the Under cash in two straight games and four of its last six contests. With the total set at 48, we're leaning towards the Under for Monday's game. San Francisco has its top RB back in Mostert, who struggled against the Rams last week but should be ready to exploit Buffalo's 22nd-ranked DVOA rush defense, which should help eat up the clock and limit Buffalo's scoring chances.
On the flip side, the Bills also showed a newfound dedication to running the ball themselves last week, gashing the Chargers for 172 yards on the ground. Against a Niners defense that has the fourth-best QB hurry percentage in the league, Buffalo will again utilize the run in order to take the pressure off Allen and limit his chances at making costly turnovers.
Lots of running, combined with a Niners defense that has allowed just one 300-yard passing performance all season, has us backing the Under Monday night.
PREDICTION: Under 48 (-101)
First Quarter Total Pick
Both of these teams are in the top half of the league in first-quarter scoring, with Buffalo second at 7.3 points and San Fran 15th with 5.5 points. The Bills have been extra-hot to start games lately, with four touchdowns in their last three first quarters.
San Francisco has also scored a TD in each of its last two opening periods, so we're looking at both teams to continue their hot starts and put up some points in the first 15 minutes on Monday.
PREDICTION: First quarter Over 9.5 (-111)
Bills vs 49ers Betting Card
- San Francisco +1 (-110)
- Under 48 (-110)
- First quarter Over 9.5 (-111)
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