Indianapolis Colts vs. Buffalo Bills Predictions, Odds, Picks

Nov. 21, 2021
Jonathan Willis
VI Betting Expert
VegasInsider.com

An AFC battle on Sunday sees the Indianapolis Colts head further north to take on the Buffalo Bills. Kickoff is set for 1:00 p.m. ET and will air on CBS from Highmark Stadium in Orchard Park, New York.

Score Prediction

Bills 30, Colts 17

Best Bets

Bills -7

Under

Indianapolis Colts vs. Buffalo Bills Predictions

The Buffalo Bills have looked like the team to beat in the AFC at times this season. Buffalo has routed most of its opponents, and the Bills brushed aside a dismal performance against Jacksonville two weeks ago with a 28-point win over the New York Jets. They are now looking to hold off the surging New England Patriots with a convincing win over the Indianapolis Colts on Sunday in Orchard Park.

Josh Allen remains the favorite to be named NFL MVP with BetMGM, despite his poor performance against Jacksonville two weeks ago. His versatility has made Buffalo a contender in the AFC, but its this defense that is the real story to the Bills’ success in 2021. They will harangue Carson Wentz throughout the day and help Buffalo win by two scores on Sunday.

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Indianapolis Colts vs. Buffalo Bills Betting Resources

  • Matchup: AFC South vs. AFC East
  • Date: Sunday, November 21, 2021
  • Venue: Highmark Stadium
  • Location: Orchard Park, New York
  • TV-Time: CBS - 1:00 p.m. ET

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Indianapolis Colts Betting Analysis

Straight Up - SU, Against the Spread - ATS, Over-Under (O/U)

  • SU: 5-5
  • ATS: 6-4
  • O/U: 6-4
  • ATS - Home: 3-3
  • ATS - Away: 3-1

The Colts are back to .500, but they haven’t been impressive. Indianapolis has yet to beat a team with a winning record, and four of this team’s wins are against the dregs of the AFC.

Wentz has averaged under 6.0 YPA in three of his last four starts. Wentz has only thrown three interceptions this season, but that number could easily be double considering the amount of bad passes he has been responsible for in his first season with the team.

Wentz has a solid No. 1 receiver in Michael Pittman Jr., but this offense is predicated on its ground game. Jonathan Taylor is soon to become the NFL’s leading rusher with 937 yards and nine touchdowns, and he is averaging 5.8 YPC. This offensive line has three probable Pro Bowl selections in Quenton Nelson, Eric Fisher, and Ryan Kelly.

Indianapolis has a mediocre defense. The Colts have a few stars, but top linebacker Darius Leonard and No. 1 cornerback Xavier Rhodes are both questionable to take the field on Sunday.

Buffalo Bills Betting Analysis

Straight Up - SU, Against the Spread - ATS, Over-Under (O/U)

  • SU: 6-3
  • ATS: 5-3-1
  • O/U: 4-5
  • ATS - Home: 2-1-1
  • ATS - Away: 3-2

Allen is performing very well in an offense tailor made for him. Allen has been somewhat boom or bust though with superb performances against both the Chiefs and the Jets but somewhat marginal showings against the Dolphins and Jaguars. He is the second leading rusher on the Bills behind Devin Singletary, and Allen is averaging 5.5 YPC.

This is a talented group of receivers. Stefon Diggs is set to make another Pro Bowl and could surpass 1,500 receiving yards this season. Emmanuel Sanders is averaging 16.8 YPR as the No. 2 receiver, while Dawson Knox is a dangerous red zone threat. Cole Beasley has the second-most receptions on Buffalo, but he is questionable to play after injuring his ribs last week.

Buffalo is averaging 31.1 PPG and 401.1 YPG, ranking in the top five in both scoring offense and total offense. The Bills aren’t turning the ball over often, but they have been fortunate in that area with just one of their seven fumbles lost.

Star Lotulelei will miss this game due to COVID, and star linebacker Tremaine Edmunds is considered questionable with a strained hamstring. This is a superb defense though with the best safety tandem in the league, and a standout cornerback in Tre’Davious White. Buffalo leads the NFL in takeaways, scoring defense, total defense, yards per play, and yards per pass attempt.


Indianapolis has covered the spread in eight of its last 10 road games. (AP)

Inside the Stats - Indianapolis Colts

  • Record: 5-5
  • Division Standing: 2nd - AFC South
  • Points Scored: 268
  • Points Allowed: 230
  • PS/G: 26.8 (8th)
  • PA/G: 23 (13th)

Inside the Stats - Buffalo Bills

  • Record: 6-3
  • Division Standing: 1st - AFC East
  • Points Scored: 280
  • Points Allowed: 135
  • PS/G: 31.1 (2nd)
  • PA/G: 15 (1st)

Key Players to Watch

  • IND: Carson Wentz - QB (212/334, 2,378 yards, 17 TD, 3 INT)
  • IND: Jonathan Taylor - RB (161 carries, 937 yards, 9 TD)
  • BUF: Josh Allen - QB (230/347, 2,602 yards, 19 TD, 6 INT)
  • BUF: Dawson Knox - TE (22 catches, 303 yards, 5 TD)

Indianapolis Colts vs. Buffalo Bills Betting Conclusion

Buffalo should have little trouble besting Indianapolis at home. The Bills are much better on defense and have a more well-rounded offense than the Colts. Indianapolis won’t be able to run the ball as well on this front seven, leading to mistakes from Wentz.

Indianapolis Colts vs. Buffalo Bills Betting Trends

  • Indianapolis has covered the spread in eight of its last 10 road games.
  • Indianapolis has gone OVER the point total in five of its last six road games when playing as the underdog.
  • Buffalo has won 10 of its last 11 home games.

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  • Use our exclusive BetMGM Bonus Code VIBONUS1500 to unlock BetMGM’s welcome offer for new sportsbook users!
  • Compare the latest NFL Odds from the best sportsbooks before placing a bet on this week's games.
  • Check out the North Carolina Sportsbooks just before they launch legal online sports betting.