| 1 | Sun Sep 7 | vs Dolphins | W33-8 | 1-0 | 1.000 | Lucas Oil Stadium · Indianapolis, IN |
| 2 | Sun Sep 14 | vs Broncos | W29-28 | 2-0 | 1.000 | Lucas Oil Stadium · Indianapolis, IN |
| 3 | Sun Sep 21 | at Titans | W41-20 | 3-0 | 1.000 | Nissan Stadium · Nashville, TN |
| 4 | Sun Sep 28 | at Rams | L20-27 | 3-1 | .750 | SoFi Stadium · Inglewood, CA |
| 5 | Sun Oct 5 | vs Raiders | W40-6 | 4-1 | .800 | Lucas Oil Stadium · Indianapolis, IN |
| 6 | Sun Oct 12 | vs Cardinals | W31-27 | 5-1 | .833 | Lucas Oil Stadium · Indianapolis, IN |
| 7 | Sun Oct 19 | at Chargers | W38-24 | 6-1 | .857 | SoFi Stadium · Inglewood, CA |
| 8 | Sun Oct 26 | vsTitans | W38-14 | 7-1 | .875 | Lucas Oil Stadium · Indianapolis, IN |
| 9 | Sun Nov 2 | at Steelers | L20-27 | 7-2 | .778 | Acrisure Stadium · Pittsburgh, PA |
| 10 | Sun Nov 9 | vs Falcons | W31-25 (OT) | 8-2 | .800 | Lucas Oil Stadium · Indianapolis, IN |
| --bye week-- |
| 12 | Sun Nov 23 | at Chiefs | L20-23 (OT) | 8-3 | .727 | Arrowhead Stadium · Kansas City, MO |
| 13 | Sun Nov 30 | vs Texans | L16-20 | 8-4 | .667 | Lucas Oil Stadium · Indianapolis, IN |
| 14 | Sun Dec 7 | at Jaguars | L19-36 | 8-5 | .615 | TIAA Bank Field · Jacksonville, FL |
| 15 | Sun Dec 14 | at Seahawks | L16-18 | 8-6 | .571 | Lumen Field · Seattle, WA |
| 16 | Mon Dec 22 | vs 49ers | L27-48 | 8-7 | .533 | Lucas Oil Stadium · Indianapolis, IN |
| 17 | Sun Dec 28 | vsJaguars | L17-23 | 8-8 | .500 | Lucas Oil Stadium · Indianapolis, IN |
| 18 | Sun Jan 4 | atTexans | L30-38 | 8-9 | .471 | NRG Stadium · Houston, TX |
