The Indianapolis Colts dominated the Buffalo Bills with a final score of 48-17 in Week 10 of the 2027 season. With this victory, the Colts solidified their playoff aspirations while the Bills struggled to find their footing in a challenging season. Baker Mayfield led the charge for Indianapolis, throwing for 281 yards and three touchdowns, showcasing his ability to connect with his weapons downfield. Jaydon Blue added a powerful ground game, rushing for 130 yards, while Josh Downs was a reliable target, racking up 85 receiving yards. The Colts' offensive efficiency was on full display as they consistently moved the ball and found the end zone. Defensively, the Colts were opportunistic, with Cam Taylor-Britt snagging an interception that turned the momentum in their favor. The game’s turning point came in the second quarter when Mayfield connected with Downs for a touchdown that extended the lead to 24-10, effectively putting the game out of reach for the Bills. Despite Greg Rousseau's strong performance with 1.5 sacks, the Bills struggled to contain the Colts' high-octane offense, leading to a lopsided defeat.