Buffalo Bills at Indianapolis Colts Best Bet | Week 10

Buffalo Bills at Indianapolis Colts Betting Preview | NFL Week 10
Where: Lucas Oil Stadium, Indianapolis, IN
When: Sunday, November 10th at 1:00 PM EST
Watch: CBS

Betting Odds
Spread: Buffalo Bills -4.0
Total: 47.5 Over/Under

This Sunday afternoon, the Buffalo Bills (7-2) take their win streak on the road to face the Indianapolis Colts (4-5) in a matchup that carries more urgency for the Colts. While the Bills sit comfortably atop the AFC East, the Colts find themselves on the playoff bubble and in need of a win to stay in the Wild Card race. Buffalo enters this matchup with one of the most balanced attacks in the league, while the Colts, struggling on defense, hope to rally behind veteran quarterback Joe Flacco, who took over the starting role. Expect a competitive game in Indianapolis as the Colts try to hold their ground against a Bills team in prime form.

Buffalo Bills

The Bills have solidified their place as AFC East leaders with a 7-2 record and are performing well on both sides of the ball. Behind Josh Allen, Buffalo’s offense averages 28.9 points per game (4th in the NFL), blending an effective passing game with a steady ground attack. Despite a mid-range ranking in passing yards, Allen’s chemistry with receivers Khalil Shakir, rookie Keon Coleman, and new addition Amari Cooper has been impressive, though Coleman and Cooper remain limited in practice. The Bills also boast a reliable ground game led by James Cook, complemented by Ray Davis. Facing a Colts defense that ranks near the bottom in rush defense, Buffalo’s run game is expected to thrive.

Defensively, the Bills rank 8th in points allowed, limiting opponents to 19.8 per game. They’ve excelled at tightening up in the red zone, and their offense’s low turnover rate has helped keep the defense out of high-risk situations. Look for the Bills to capitalize on the Colts’ defensive weaknesses and control the game tempo.

Indianapolis Colts

The Colts have hit a rough patch, now 4-5 after back-to-back losses, but remain competitive in the AFC South. Indianapolis has made the switch to veteran quarterback Joe Flacco, with Anthony Richardson struggling and showing limited development. Flacco has brought more stability, but the offense primarily leans on running back Jonathan Taylor, who is expected to see a significant workload. Taylor’s health has fluctuated this season, but he appears fully recovered and ready to take on the Bills’ defense.

Defensively, the Colts have struggled across the board, ranking 25th or worse in total yards allowed, rush defense, and pass defense. Despite these metrics, they’ve managed to keep points allowed to 21.4 per game. However, their inability to get off the field on third down (43.7% conversion rate) has been a major weakness, one that could be exploited by Buffalo’s efficient offense.

My Pick: Buffalo Bills -4.0 (-110)

Buffalo has the clear edge in this matchup, with the weapons to expose the Colts’ defensive vulnerabilities in both the run and passing games. Indianapolis has not faced a team of Buffalo’s caliber at home, and despite a slight home-field advantage, they lack the firepower to keep pace. Expect a comfortable Bills win, with James Cook likely to have a big day on the ground, including a potential touchdown.