| 1 | Mon Sep 9 | at Saints | L28-30 | 0-1 | .000 | Caesars Superdome · New Orleans, LA |
| 2 | Sun Sep 15 | vsJaguars | W13-12 | 1-1 | .500 | NRG Stadium · Houston, TX |
| 3 | Sun Sep 22 | atChargers | W27-20 | 2-1 | .667 | SoFi Stadium · Inglewood, CA |
| 4 | Sun Sep 29 | vsPanthers | L10-16 | 2-2 | .500 | NRG Stadium · Houston, TX |
| 5 | Sun Oct 6 | vsFalcons | W53-32 | 3-2 | .600 | NRG Stadium · Houston, TX |
| 6 | Sun Oct 13 | atChiefs | W31-24 | 4-2 | .667 | Arrowhead Stadium · Kansas City, MO |
| 7 | Sun Oct 20 | atColts | L23-30 | 4-3 | .571 | Lucas Oil Stadium · Indianapolis, IN |
| 8 | Sun Oct 27 | vsRaiders | W27-24 | 5-3 | .625 | NRG Stadium · Houston, TX |
| 9 | Sun Nov 3 | atJaguars | W26-3 | 6-3 | .667 | Wembley Stadium · London, England |
| --bye week-- |
| 11 | Sun Nov 17 | atRavens | L7-41 | 6-4 | .600 | M&T Bank Stadium · Baltimore, MD |
| 12 | Thu Nov 21 | vsColts | W20-17 | 7-4 | .636 | NRG Stadium · Houston, TX |
| 13 | Sun Dec 1 | vsPatriots | W28-22 | 8-4 | .667 | NRG Stadium · Houston, TX |
| 14 | Sun Dec 8 | vsBroncos | L24-38 | 8-5 | .615 | NRG Stadium · Houston, TX |
| 15 | Sun Dec 15 | atTitans | W24-21 | 9-5 | .643 | Nissan Stadium · Nashville, TN |
| 16 | Sat Dec 21 | atBuccaneers | W23-20 | 10-5 | .667 | Raymond James Stadium · Tampa, FL |
| 17 | Sun Dec 29 | vsTitans | L14-35 | 10-6 | .625 | NRG Stadium · Houston, TX |
| WC | Sat Jan 4 | vsBills | W22-19 (OT) | 10-6 | .625 | NRG Stadium · Houston, TX |
| DIV | Sun Jan 12 | atChiefs | L31-51 | 10-6 | .625 | Arrowhead Stadium · Kansas City, MO |
