Tom Brady threw three touchdowns for New England, while two throws from opposite number Andrew Luck were returned for scores by Aqib Talib and Alfonzo Dennard.
It was a fourth straight win for the Patriots, who are now 7-3.
The Colts had entered the game on a four-game winning streak.
The New Orleans Saints continued their revival with a 38-17 victory over the Oakland Raiders, lifting them back to .500.
Drew Brees threw three touchdown passes as New Orleans won a third straight game.
Peyton Manning threw for three touchdowns as the Denver Broncos beat the San Diego Chargers 30-23, moving three games clear in the AFC West.
It was Manning's 148th regular-season win as a starting quarterback, which ties him with John Elway in second place. Brett Favre has 186.
The Pittsburgh Steelers scored the opening touchdown on a 31-yard run from Byron Leftwich inside the first minute of the game but ended up 13-10 losers against the Baltimore Ravens, who have taken control of the AFC North with the win.
Jacoby Jones returned a punt for a touchdown and Justin Tucker had two field goals for Baltimore.