| 1 | Sun Sep 8 | at Chargers | L24-30 (OT) | 0-1 | .000 | SoFi Stadium · Inglewood, CA |
| 2 | Sun Sep 15 | atTitans | W19-17 | 1-1 | .500 | Nissan Stadium · Nashville, TN |
| 3 | Sun Sep 22 | vsFalcons | W27-24 | 2-1 | .667 | Lucas Oil Stadium · Indianapolis, IN |
| 4 | Sun Sep 29 | vsRaiders | L24-31 | 2-2 | .500 | Lucas Oil Stadium · Indianapolis, IN |
| 5 | Sun Oct 6 | atChiefs | W19-13 | 3-2 | .600 | Arrowhead Stadium · Kansas City, MO |
| --bye week-- |
| 7 | Sun Oct 20 | vsTexans | W30-23 | 4-2 | .667 | Lucas Oil Stadium · Indianapolis, IN |
| 8 | Sun Oct 27 | vsBroncos | W15-13 | 5-2 | .714 | Lucas Oil Stadium · Indianapolis, IN |
| 9 | Sun Nov 3 | atSteelers | L24-26 | 5-3 | .625 | Acrisure Stadium · Pittsburgh, PA |
| 10 | Sun Nov 10 | vsDolphins | L12-16 | 5-4 | .556 | Lucas Oil Stadium · Indianapolis, IN |
| 11 | Sun Nov 17 | vsJaguars | W33-13 | 6-4 | .600 | Lucas Oil Stadium · Indianapolis, IN |
| 12 | Thu Nov 21 | atTexans | L17-20 | 6-5 | .545 | NRG Stadium · Houston, TX |
| 13 | Sun Dec 1 | vsTitans | L17-31 | 6-6 | .500 | Lucas Oil Stadium · Indianapolis, IN |
| 14 | Sun Dec 8 | atBuccaneers | L35-38 | 6-7 | .462 | Raymond James Stadium · Tampa, FL |
| 15 | Mon Dec 16 | atSaints | L7-34 | 6-8 | .429 | Caesars Superdome · New Orleans, LA |
| 16 | Sun Dec 22 | vsPanthers | W38-6 | 7-8 | .467 | Lucas Oil Stadium · Indianapolis, IN |
| 17 | Sun Dec 29 | atJaguars | L20-38 | 7-9 | .438 | TIAA Bank Field · Jacksonville, FL |
