Indianapolis Colts at Buffalo Bills Picks & Betting Predictions

The Buffalo Bills rebounded from a horrific 9-6 loss to the woeful Jacksonville Jaguars to crush the equally woeful New York Jets in Week 10. Back home for this one, Buffalo finds itself dealing with a resurgent Indianapolis Colts team in the NFL betting lines.

Indy is 4-1 over the past five games. Heading to Buffalo, though, they aren’t getting much love. On NFL betting apps, the Colts are 7-point road underdogs in the NFL picks.

Take a look at Bills vs. Colts odds, injury report, betting lines and more.

Colts vs Bills Key Matchups

Who Will Take It Away?: The Bills lead the NFL in takeaways (+14). The Colts are second in this category (+11). Which opportunistic defense will enjoy the most productive day?

Colts RB Jonathan Taylor vs Buffalo defense: Taylor shares the NFL rushing lead with 973 yards. The Bills are the NFL’s No. 1 defense.

Indy vs Good Teams: Buffalo is 5-1 this season against teams that don’t have winning records. The Colts are 5-5. Indy is 0-4 against teams with winning records. Buffalo is 6-3.

RELATED: NFL Week 11 Odds & Betting Lines For All Games

5 Key Colts vs Bills Stats

10+ points: Margin of victory for the Bills in each of their last 13 victories.

7: Number of consecutive games in which Colts RB Jonathan Taylor has a rushing TD and 100+ scrimmage yards gained.

6: Number of TD passes allowed by the Buffalo defense. That’s the lowest total in the NFL.

5-0: Indy’s record when Taylor gains 100 yards on the ground. The Colts are 0-5 when he doesn’t get 100 yards.

4-0: Buffalo’s record at home against Indianapolis since 2010.

Colts vs Bills Weather Forecast

It’s always a bit of a challenge for a dome team like the Colts to play outdoors. That’s especially true for later-season games in cold-weather sites such as Buffalo. Fortunately, it appears as though the weather at Highmark Stadium will be somewhat balmy for the third week of November. The forecast is calling for clouds, 14 mph wind and a game-time temperature of 47 degrees.

Colts vs Bills Player Props

Bills TE Dawson Knox over 35.5 receiving yards

Odds: -115 at Caesars

Indy is the sixth-worst NFL team at defending the TE. KC is No. 5 and Knox went off for a season-high 117 yards against the Chiefs.

Bet $1, Double Your Winnings Your Next 10 Bets Promo Code: BOOKIESDYW

Tap for Promo Activated! Visit site

Used 7 Times Today

Must be 21+ to participate. T&Cs apply.

Colts RB Jonathan Taylor over 73.50 rushing yards

Odds: -115 at Caesars

Taylor has bettered this number in four of the past five games.

Bills QB Josh Allen over 6.5 rushing attempts

Odds: -110 at Caesars

Allen has gone over 6.5 carries in three of his last five games.

RELATED: NFL Week 11 Picks & Best Bets For Every Game

Colts vs Bills Moneyline

The Colts have dropped four in a row at Buffalo. Overall, Buffalo has won three of the past four meetings between the two teams. Indy’s 0-4 mark against teams with winning records this season is also alarming. The Bills are 3-1 straight up at home this season and an NFL-best 12-2 SU at home since the beginning of the 2020 season.

Indianapolis is 2-2 SU as an away team this season and 7-6 since the start of last season. As much as it’s logical to play the Bills on the moneyline at NFL betting sites, the fact of the matter is that at -310, it simply won’t be profitable enough for it to be a worthwhile wager.

$1,500 Paid Back in Bonus Bets If You Don't Win Promo Code: BOOKIES

Tap for Promo Activated! Visit site

Used 44 Times Today

Bonus Bets Expire in 7 Days. One New Customer Offer Only. Must be 21+ to participate. Gambling problem? Call 1-800-GAMBLER (CO, DC, IL, IN, KY, LA, MD, MS, NC, NJ, OH, PA, TN, VA, WV, WY) Call 877-8-HOPENY or text HOPENY (467369) (NY). Call 1-800-NEXT-STEP (AZ), 1-800-522-4700 (KS, NV), 1-800-327-5050 (MA), 1-800-BETS-OFF (IA), 1-800-270-7117 for confidential help (MI). Visit BetMGM.com for T&Cs. US promotional offers not available in NY, NV, or Puerto Rico.

Colts vs Bills Point Spread

At 6-4 against the spread this season, only five NFL teams are showing a better ATS record this season than the Colts. Indy is also 3-0 ATS in its last three games as a road underdog. That being said, Indy failed to cover against the Jacksonville Jaguars last week. Then again, the Bills lost outright to the Jags the week before, so maybe that’s not the best measurable to be applying here.

At home, the Bills are 7-2-1 ATS in their last 10 games. Buffalo is 6-4-1 ATS in the last 11 games that the club was a seven-point pick in NFL spreads.

While progress continues to be made on online sports betting in New York, a launch is not expected until around the time of the Super Bowl. Still, Bills backers who are able to get a wager down this weekend should take Buffalo and lay the 7 points at DraftKings.

Bet $5, Get $200 in Bonus Bets Instantly

Tap for Promo Activated! Visit site

Used 18 Times Today

GAMBLING PROBLEM? CALL 1-800-GAMBLER, (800) 327-5050 or visit gamblinghelplinema.org (MA). Call 877-8-HOPENY/text HOPENY (467369) (NY). Please Gamble Responsibly. 888-789-7777/visit ccpg.org (CT), or visit www.mdgamblinghelp.org (MD). 21+ and present in most states. (18+ DC/KY/NH/WY). Void in ONT/OR/NH. Eligibility restrictions apply. On behalf of Boot Hill Casino & Resort (KS). 1 per new customer. $5+ first-time bet req. Max. $200 issued as non-withdrawable Bonus Bets that expire in 7 days (168 hours). Stake removed from payout. Terms: sportsbook.draftkings.com/promos. Ends 5/18/25 at 11:59 PM ET. Sponsored by DK.

Colts vs Bills Totals

The total is 1-3 in four Buffalo home games this season. The total for this game is set at 50 points. Interestingly, on the two occasions thus far this season in which sportsbooks have set the total on a Bills game at 50 or more points, the over is 2-0.

In fact, the over is 6-3 in the nine times the total was at 50 or more points on a Buffalo game. As well, the total has gone over in six of Indy’s last seven road games. Go with the over as the call on this wager. You can get Over 50 (-110) at FanDuel.

Bet $5, Get $200 in Bonus Bets if Your Bet Wins!

Tap for Promo Activated! Visit site

Used 21 Times Today

Must be 21+ to participate. Gambling Problem? Call 1-800-GAMBLER or visit FanDuel.com/RG (CO, IA, KY, MI, NJ, OH, PA, IL, TN, VA, VT), 1-800-NEXT-STEP or text NEXTSTEP to 53342 (AZ), 1-888-789-7777 or visit ccpg.org/chat (CT), 1-800-9-WITH-IT (IN), 1-800-522-4700 or visit ksgamblinghelp.com (KS), 1-877-770-STOP (LA), visit www.mdgamblinghelp.org (MD), 1-800-522-4700 (WY), or visit www.1800gambler.net (WV). GamblingHelpLineMA.org or call (800) 327-5050 for 24/7 support (MA). Call 1-877-8HOPE-NY or text HOPENY (467369) (NY).