| Date | Wk | Side | Opponent | Score | Result | Spread | O/U | Stadium |
|---|---|---|---|---|---|---|---|---|
| 2025-09-07 | 1 | vs | MIA | 33-8 | W | 1.5 | 47.5 | Lucas Oil Stadium |
| 2025-09-14 | 2 | vs | DEN | 29-28 | W | -2.5 | 43.5 | Lucas Oil Stadium |
| 2025-09-21 | 3 | @ | TEN | 41-20 | W | -6 | 43.5 | Nissan Stadium |
| 2025-09-28 | 4 | @ | LA | 20-27 | L | 3.5 | 49.5 | SoFi Stadium |
| 2025-10-05 | 5 | vs | LV | 40-6 | W | 7 | 46.5 | Lucas Oil Stadium |
| 2025-10-12 | 6 | vs | ARI | 31-27 | W | 8.5 | 46.5 | Lucas Oil Stadium |
| 2025-10-19 | 7 | @ | LAC | 38-24 | W | 2.5 | 48.5 | SoFi Stadium |
| 2025-10-26 | 8 | vs | TEN | 38-14 | W | 15.5 | 47.5 | Lucas Oil Stadium |
| 2025-11-02 | 9 | @ | PIT | 20-27 | L | -3.5 | 51.5 | Acrisure Stadium |
| 2025-11-09 | 10 | vs | ATL | 31-25 | W | 6.5 | 48.5 | Lucas Oil Stadium |
| 2025-11-23 | 12 | @ | KC | 20-23 | L | 3.5 | 50.5 | GEHA Field at Arrowhead Stadium |
| 2025-11-30 | 13 | vs | HOU | 16-20 | L | 3 | 44.5 | Lucas Oil Stadium |
| 2025-12-07 | 14 | @ | JAX | 19-36 | L | -2.5 | 44.5 | TIAA Bank Stadium |
| 2025-12-14 | 15 | @ | SEA | 16-18 | L | 13.5 | 41.5 | Lumen Field |
| 2025-12-22 | 16 | vs | SF | 27-48 | L | -4.5 | 46.5 | Lucas Oil Stadium |
| 2025-12-28 | 17 | vs | JAX | 17-23 | L | -3.5 | 48.5 | Lucas Oil Stadium |
| 2026-01-04 | 18 | @ | HOU | 30-38 | L | 9.5 | 37.5 | NRG Stadium |
