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49ers vs. Bills Early Picks, Predictions & Odds for SNF Week 13

Mike Spector

Last Updated: November 25, 2024 8:28 AM EST • 3 min 35 sec read.

Buffalo Bills quarterback Josh Allen runs with the ball as we make our 49ers vs. Bills Week 13 Sunday Night Football (SNF) early picks.
Buffalo Bills quarterback Josh Allen runs with the ball for a first down. Photo by Gregory Fisher-Imagn Images.

The San Francisco 49ers have several key players on both sides of the ball on the injury report ahead of their Week 13 Sunday Night Football matchup with the Buffalo Bills.

  • The 49ers are off to their worst start (5-6) since 2020
  • The Bills are off a bye week after handing the Kansas City Chiefs their only loss of the season in Week 11
  • San Francisco was without QB Brock Purdy, LT Trent Williams, and DE Nick Bosa, among others, in its Week 12 loss to Green Bay

Our 49ers vs. Bills early picks and odds make a cautious play on the home favorites, knowing that much of the opinion on this game can change based on how the injury report shakes out.

My early 49ers vs. Bills prediction: Bills -6.5

NFL picks made Sunday; odds subject to change. Our NEW NFL player prop odds tool can help you find the best odds on any market across legal sportsbooks in your area!

Prediction: Bills -6.5

Best odds: | Implied probability: 52.38%

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The last time we saw the Bills in action was two weeks ago. They broke Kansas City’s streak of not allowing 30 points, something it had done since Week 4 of the 2020 season. Buffalo also held Kansas City to its fewest total yards (259) since 2021.

The Bills are 5-0 at home for the first time since 1995, and have averaged 29.7 points per game during a six-game winning streak.

It is fair to wonder what San Francisco’s motivation level will be if players like Purdy and Bosa are once again ruled out. Last week, it looked lifeless in a 28-point loss—its worst since 2018—and I am comfortable laying anything less than a touchdown before getting more clarity on each team’s injury news.

Don't miss our guide for how to bet on NFL or this week's best sportsbook promos.

49ers vs. Bills live odds

See the NFL odds from our best NFL betting sites for every Week 13 game.

Moneyline

  • Bills best odds: -275 via BetMGM | Implied probability: 73.33%
  • 49ers best odds: +250 via DraftKings | Implied probability: 28.57%

As expected, there is a big 35-cent gap between BetMGM’s -275 moneyline odds and the -310 at DraftKings on the high end of the market, as the top sports betting sites differ in how they are baking in San Francisco’s potential injuries.

San Francisco may be in last place in the NFC West, but it is still just one game out of first place. The 49ers should get plenty of moneyline support if Purdy and Bosa are declared active this week, given that they have overcome similar slow starts as this one to make deep playoff runs in recent years.

Spread

  • Bills best odds: -6.5 (-110) via DraftKings
  • 49ers best odds: +7 (-110) via Caesars

Caesars is the only one of our top sports betting sites that has moved from Bills -6.5 to -7, as it likely wants to get out ahead of any negative 49ers injury news that would dictate moving the line further.

To put this line movement in perspective, Green Bay opened as a 2.5-point favorite over San Francisco last week, and the line ballooned to -5.5 once Purdy was ruled out.

Given that the Packers beat the 49ers by 28 with Purdy out and that the Bills are considered a superior team to Green Bay, our best sports betting apps would likely move to -7.5 or higher if Brandon Allen is again under center.

At one point, Purdy was considered day-to-day last week with his shoulder injury, but bettors should be scouring the reports from the team’s beat writers and insiders to get ahead of the oddsmakers.

Over/Under

  • Over best odds: 46 (-110) via BetMGM
  • Under best odds: 46.5 (-115) via FanDuel

Buffalo has scored 30 or more points in five consecutive games for the third time in franchise history. That alone should keep this total from plummeting, no matter how the 49ers injury report shakes out.

The Over has cashed in all of Buffalo’s five home games. In addition, both teams are profitable to the Over. San Francisco has a 6-5 O/U record, and Buffalo has cashed the Over in seven of its 11 games.

This total has more room to significantly increase based on positive injury news than it would plummet if San Francisco’s actives are similar to what it had in Week 12.

How to watch 49ers vs. Bills

  • When: Sunday, Dec. 1
  • Kickoff: 8:20 p.m. ET
  • Where: Highmark Stadium (Orchard Park, N.Y.)
  • How to watch: NBC/Peacock
  • Weather: 34 degrees, 25% chance of precipitation, wind 7 mph WSW
  • Favorite: Bills -6.5 (-115 via BetMGM)

NFL betting odds pages

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Written By:
Mike Spector
Mike started in the sports writing industry in July 2019, and gained a lot of followers in his first year after finishing with the No. 2 overall record in an annual NFL betting competition, which made picks against the spread, and from an Over/Under and moneyline perspective. Mike is an avid fan of the NFL, MLB, tennis, and all college sports. In his opinion, March Madness is the best sporting event there is, and he's especially euphoric starting with conference tournament time in college basketball. Mike's a big advocate of "fading the public" and making plays that are contrarian, constantly citing that "there are reasons why they have those big shiny buildings in Las Vegas." When making wagers, Mike always scours the best odds at all of the major sports betting sites, where he mostly sifts through DraftKings, FanDuel, BetMGM, and bet365. He's tried several others and is of the firm belief that bettors should not just stick to one sportsbook, as there is always likely better value to be had with the same wager. In addition, while Mike received his undergraduate degree from Villanova University, he has no issue betting against the Wildcats when it comes to college basketball wagering, and suggests other bettors should always put their “head” before their “hearts.”