The Texans turned the ball over twice in the first quarter and quarterback Tyrod Taylor was benched in the third quarter as Houston (2-10) lost for the ninth time in 10 games.
Jonathan Taylor, who leads the NFL in yards rushing, has 16 rushing touchdowns this season, which ties the franchise record set by Lenny Moore in 1964. It's the 10th straight game where he's ran for a touchdown, the longest streak in the NFL since LaDainian Tomlinson did it in 18 straight in the 2004 and 2005 seasons.
Things went wrong for Houston immediately with Tyrod Taylor throwing an interception on the team's first play. It was initially ruled an incompletion, but the Colts challenged the call and the review showed that Kenny Moore grabbed it just before falling out of bounds.
The Colts took a 7-0 lead when Jonathan Taylor took the snap out of the wildcat and ran 1 yard for the score.
The second big mistake by the Texans came on the fourth play of the next drive when Pharaoh Brown fumbled after a catch and it was recovered by the Colts.
They failed to capitalize on that mistake when Michael Badgley's 35-yard field goal sailed wide left.
Indianapolis extended the lead to 14-0 when Wentz found Ashton Dulin in the corner of the end zone for a 2-yard touchdown just before halftime. The Colts kept that drive alive on a sneak by Wentz on fourth-and-1.
Jonathan Taylor's second TD run came on the opening possession of the third quarter to push the lead to 21-0. It was a 3-yard run that capped a 75-yard drive.
Tyrod Taylor was evaluated for an undisclosed injury after Houston's first possession of the third quarter, but the team said he was available to play, and it was coach David Culley's decision to insert backup Davis Mills in his place. He was 5 for 13 for 45 yards before being replaced.
After the two early turnovers, the Texans punted on four consecutive drives before Mills entered the game with about four minutes left in the third quarter. The QB change didn't do anything to help Houston's offense and the Texans punted twice after Mills took over and turned the ball over on downs on his other three possessions.
Mills was 6 of 14 for 49 yards.
The boos from the sparse crowd began early and grew louder with each terrible offensive possession as the Texans were shut out for the second time this season. It's their second loss to the Colts this year after they got a 31-3 victory in Indianapolis in October.
The Colts outgained Houston 389-141 and Indianapolis had 26 first downs to just 9 by the Texans.
A 23-yard field goal with about nine minutes left made it 24-0 and rookie Deon Jackson added a 3-yard TD run with two minutes to go.
Colts: Have a bye next week and host New England Dec. 18.
Texans: Host Seattle next Sunday.