| 2025-09-07 | 1 | vs |  TEN | 20-12 | W | 8.5 | 42.5 | Empower Field at Mile High |
| 2025-09-14 | 2 | @ |  IND | 28-29 | L | -2.5 | 43.5 | Lucas Oil Stadium |
| 2025-09-21 | 3 | @ |  LAC | 20-23 | L | 2.5 | 45.5 | SoFi Stadium |
| 2025-09-29 | 4 | vs |  CIN | 28-3 | W | 7.5 | 44.5 | Empower Field at Mile High |
| 2025-10-05 | 5 | @ |  PHI | 21-17 | W | 3.5 | 44.5 | Lincoln Financial Field |
| 2025-10-12 | 6 | @ |  NYJ | 13-11 | W | -7.5 | 43.5 | MetLife Stadium |
| 2025-10-19 | 7 | vs |  NYG | 33-32 | W | 7.5 | 39.5 | Empower Field at Mile High |
| 2025-10-26 | 8 | vs |  DAL | 44-24 | W | 3.5 | 51.5 | Empower Field at Mile High |
| 2025-11-02 | 9 | @ |  HOU | 18-15 | W | 1.5 | 40.5 | NRG Stadium |
| 2025-11-06 | 10 | vs |  LV | 10-7 | W | 9.5 | 42.5 | Empower Field at Mile High |
| 2025-11-16 | 11 | vs |  KC | 22-19 | W | -3.5 | 44.5 | Empower Field at Mile High |
| 2025-11-30 | 13 | @ |  WAS | 27-26 | W | -6.5 | 43.5 | FedExField |
| 2025-12-07 | 14 | @ | LV | 24-17 | W | -8.5 | 40.5 | Allegiant Stadium |
| 2025-12-14 | 15 | vs |  GB | 34-26 | W | -1.5 | 42.5 | Empower Field at Mile High |
| 2025-12-21 | 16 | vs |  JAX | 20-34 | L | 3.5 | 46.5 | Empower Field at Mile High |
| 2025-12-25 | 17 | @ | KC | 20-13 | W | -13.5 | 37.5 | GEHA Field at Arrowhead Stadium |
| 2026-01-04 | 18 | vs | LAC | 19-3 | W | 14.5 | 37.5 | Empower Field at Mile High |
| 2026-01-17 | 20 | vs |  BUF | 33-30 | W | 1.5 | 45.5 | Empower Field at Mile High |
| 2026-01-25 | 21 | vs |  NE | 7-10 | L | -3.5 | 43.5 | Empower Field at Mile High |
