This year’s Thanksgiving Day NFL tripleheader concludes with an interesting cross-conference matchup between the Buffalo Bills and New Orleans Saints. Both teams were sitting pretty as far as their respective playoff races just a few weeks ago. After two embarrassing losses in a three-week span, the Bills are now barely clinging to an AFC Wild Card spot. Meanwhile, the Saints have also dropped two straight and are one of the most injured teams in the league. Only one side will be able to get things back on track this week. The NFL betting odds have set the visitors as favorites of nearly a full touchdown ahead of this Bills vs Saints primetime showdown.

The following Bills vs Saints NFL betting preview will give you the current odds, betting trends and picks for the Week 12 Thanksgiving Day matchup, along with a stream link to watch games all season long.


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Bills vs Saints Week 12 Thanksgiving Day NFL Betting Preview

NFL Regular Season — Week 12 Thanksgiving Day
Buffalo Bills (6-4, 3-2 Away) vs. New Orleans Saints (5-5, 2-2 Home)
Date: Thursday, Nov. 25, 2021
Time: 8:20 p.m. EST
Venue: Caesars Superdome — New Orleans, LA
Coverage: Click here for the stream

Buffalo Bills Preview

The Bills went into Week 11 as NFL betting favorites to win the Super Bowl. Well, that is no longer the case after suffering a beatdown at home courtesy of Jonathan Taylor and the Indianapolis Colts. Josh Allen threw two more interceptions on Sunday and looks much more like his pre-2020 self than the player who was an MVP candidate last year and inked a massive contract extension in the offseason. The Bills also have major issues to fix along both the offensive and defensive fronts. An inability to run the football has the offense looking extremely one-dimensional. Meanwhile, Buffalo’s run defense looks just as bad as it did a year ago.

When it comes to offensive firepower in this Thanksgiving NFL betting showdown, the Bills have a clear advantage. Nothing comes easy against the Saints’ defense, but Allen should be able to move the ball thanks to the loaded receiving corps of Stefon Diggs, Emmanuel Sanders and Cole Beasley. A measure of redemption figures to be on the minds of all Bills players this week after last week’s disastrous performance. Knowing that the Saints are down to a backup quarterback in Trevor Siemian, it’s also worth noting that Buffalo’s defense has forced 24 turnovers this season, the second-most in the NFL.

New Orleans Saints Preview

No team has been hit harder by injuries this season than the Saints. The loss of starting quarterback Jameis Winston to a torn ACL will be felt for the remainder of the year. The injury bug has spread further than that, however. In total, New Orleans was without seven offensive starters in last week’s loss to the Philadelphia Eagles. Star running back Alvin Kamara is set to miss his third straight game after being ruled out for this Thanksgiving night NFL betting showdown. Fellow RB Mark Ingram carries a questionable designation of his own into gameday. On the bright side, the Saints do expect to have offensive tackle Terron Armstead back after he participated fully in Tuesday’s practice. 

With the offensive injuries being numerous for New Orleans, hopes of a Turkey Day upset and any sort of postseason run lie on the shoulders of the defense. The Saints should have no issues stuffing the Bills’ non-existent rushing attack given that they boast the top adjusted run defense in the NFL. The secondary will face a tall task holding up against the stacked Bills receiving corps. However, the Saints have been one of the NFL’s best defenses when it comes to generating takeaways and could thrive against a suddenly turnover-prone Buffalo team.

Credit: USA TODAY Sports

Bills vs Saints Odds and Spread

NFL betting odds for Bills vs Saints are taken from BetMGM Sportsbook.

Moneyline: BUF: (-250) | NO: (+210)
Spread: BUF: -6 (-110) | NO: +6 (-110)
Total: 45.5 — Over: (-110) | Under: (-110)
Public (Spread) Betting Percentages via Action Network: BUF: (64%) | NO: (36%)

Bills vs Saints NFL Betting Trends

  • Bills are 7-0 ATS in their last seven games against NFC opponents.
  • The total has gone over in ten of the Bills’ last 14 road games.
  • Six of the Saints’ last seven games have gone over the total.
  • Saints are 14-3 straight up in their last 17 games against AFC opponents.
  • Saints are 5-0 both straight up and ATS in their last five head-to-head matchups against the Bills.

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Bills vs Saints Stats

  • Buffalo is averaging 29.5 points per game (PPG) this season (No. 2 in the NFL).
  • Buffalo is surrendering 17.6 PPG this season (No. 2 in the NFL).
  • New Orleans is averaging 25.1PPG this season (No. 14 in the NFL).
  • New Orleans is surrendering 21.5 PPG this season (No. 10 in the NFL).

Bills vs Saints Prediction

This Bills vs Saints NFL betting prediction uses NumberFire’s game projections. They give Buffalo a 59.8% chance to win this Week 12 matchup.


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Henry’s passion for sports dates all the way back to childhood and has ultimately led to a full-fledged career as an analyst and content creator. After getting his start penning fantasy football articles, he forrayed into the betting side of the business in early 2019. His love for sports and statistics proved to be an ideal match with the dedicated research and strategy that handicapping requires. Henry currently specializes in betting analysis and picks for college football, college basketball and NASCAR. He counts the NFL, the WNBA, and NBA player props as additional leagues/markets of interest. Henry graduated from SUNY Buffalo in 2021 with a Communication Studies degree and a Psychology minor. A native of the Finger Lakes region in Upstate New York, he and his pup, Harold, have since relocated to Laramie, Wyoming. Thanks to his professional goals within the sports betting industry, there has been a whole lot of steam on the odds for a move to Las Vegas in 2023! Most of Henry’s free time is spent on outdoor adventures, playing chess, snowboarding, or reading a good book. He is also a competitive powerlifter and aspires to qualify for the USAPL Nationals meet within the next 2-3 years.

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