| 1 | Sun Sep 8 | at Colts | W29-27 | 1-0 | 1.000 | Lucas Oil Stadium · Indianapolis, IN |
| 2 | Sun Sep 15 | vsBears | W19-13 | 2-0 | 1.000 | NRG Stadium · Houston, TX |
| 3 | Sun Sep 22 | atVikings | L7-34 | 2-1 | .667 | U.S. Bank Stadium · Minneapolis, MN |
| 4 | Sun Sep 29 | vsJaguars | W24-20 | 3-1 | .750 | NRG Stadium · Houston, TX |
| 5 | Sun Oct 6 | vsBills | W23-20 | 4-1 | .800 | NRG Stadium · Houston, TX |
| 6 | Sun Oct 13 | atPatriots | W41-21 | 5-1 | .833 | Gillette Stadium · Foxborough, MA |
| 7 | Sun Oct 20 | atPackers | L22-24 | 5-2 | .714 | Lambeau Field · Green Bay, WI |
| 8 | Sun Oct 27 | vsColts | W23-20 | 6-2 | .750 | NRG Stadium · Houston, TX |
| 9 | Thu Oct 31 | atJets | L13-21 | 6-3 | .667 | MetLife Stadium · East Rutherford, NJ |
| 10 | Sun Nov 10 | vsLions | L23-26 | 6-4 | .600 | NRG Stadium · Houston, TX |
| 11 | Mon Nov 18 | atCowboys | W34-10 | 7-4 | .636 | AT&T Stadium · Arlington, TX |
| 12 | Sun Nov 24 | vsTitans | L27-32 | 7-5 | .583 | NRG Stadium · Houston, TX |
| 13 | Sun Dec 1 | atJaguars | W23-20 | 8-5 | .615 | TIAA Bank Field · Jacksonville, FL |
| --bye week-- |
| 15 | Sun Dec 15 | vsDolphins | W20-12 | 9-5 | .643 | NRG Stadium · Houston, TX |
| 16 | Sat Dec 21 | atChiefs | L19-27 | 9-6 | .600 | Arrowhead Stadium · Kansas City, MO |
| 17 | Wed Dec 25 | vsRavens | L2-31 | 9-7 | .563 | NRG Stadium · Houston, TX |
| WC | Sat Jan 11 | vsChargers | W32-12 | 10-7 | .588 | NRG Stadium · Houston, TX |
| DIV | Sat Jan 18 | atChiefs | L14-23 | 10-7 | .588 | Arrowhead Stadium · Kansas City, MO |
