Philip Rivers passed for 262 yards and three touchdowns as the Colts crushed the Lions 41-21 in Detroit.
It's the Lions seventh straight home loss, dating to last season, as they are now 0-and-3 at home this season and missed an opportunity to win three in a row for the first time with coach Matt Patricia.
Nyheim Hines caught two scores and Jordan Wilkins added 89 yards and a TD on the ground for Indianapolis.
Kenny Moore the Second returned an interception 29 yards for a score early in the fourth quarter to extend the Colts' lead to 35-14.
Lions quarterback Matthew Stafford threw for 336 yards, three TD's and the one pick for Detroit.
The Lions had just 29 yards rushing as a team on 13 carries.
Indy is now 5-and-2 while Detroit is 3-and-4 overall.
With files from the Associated Press