In the first half, Texans fans finally got a taste of the new quarterback-receiver connection between C.J. Stroud and Stefon Diggs.
At halftime, Texans led 12-7 over the Colts.
The Texans' offense heated up early in the fourth quarter, when Stroud connected with another newcomer in running back Joe Mixon for the three-yard touchdown, giving Houston a 22-13 lead.
The Stroud-Diggs connection was evident as No. 7 connected with Diggs for a two-yard touchdown.
"He showed up in the big-time moments. Got a touchdown for us. That's who he's been, right? And I'm excited to have him, and he shows what he can do for us," Texans head coach DeMeco Ryans said after the game.
Furthermore, Diggs achieved a career milestone. The Texans' star wideout cracked 10,000 yards worth of passes in his NFL career.
For the Colts, starting quarterback Anthony Richardson and his crew managed to cut the deficit 29-27 with about two minutes left in the fourth quarter.
"This is Week 1, everybody's rusty. We are - everybody's rusty. I'm not going to name any names, but I think that you can come out Week 1 and get a W against a divisional opponent; it's huge," Stroud said after assessing his performance in Week 1.
Overall, Houston survived a nail-biter against Indianapolis with a victory over an AFC South rival.
In Week 2, the Texans will go back home at NRG Stadium when the team hosts Caleb Williams and the Chicago Bears on Sept. 15.