| 2010-09-12 | 1 | @ |  JAX | 17-24 | L | 3 | 41.5 | EverBank Field |
| 2010-09-19 | 2 | vs |  SEA | 31-14 | W | 3.5 | 41 | Invesco Field at Mile High |
| 2010-09-26 | 3 | vs |  IND | 13-27 | L | -5.5 | 47 | Invesco Field at Mile High |
| 2010-10-03 | 4 | @ |  TEN | 26-20 | W | 6 | 43.5 | LP Field |
| 2010-10-10 | 5 | @ |  BAL | 17-31 | L | 8 | 39.5 | M&T Bank Stadium |
| 2010-10-17 | 6 | vs |  NYJ | 20-24 | L | -3.5 | 43 | Invesco Field at Mile High |
| 2010-10-24 | 7 | vs |  OAK | 14-59 | L | 7 | 43 | Invesco Field at Mile High |
| 2010-10-31 | 8 | @ |  SF | 16-24 | L | 2 | 41 | Wembley Stadium |
| 2010-11-14 | 10 | vs |  KC | 49-29 | W | -1 | 44 | Invesco Field at Mile High |
| 2010-11-22 | 11 | @ |  SD | 14-35 | L | 9 | 50 | Qualcomm Stadium |
| 2010-11-28 | 12 | vs |  STL | 33-36 | L | 3 | 46.5 | Invesco Field at Mile High |
| 2010-12-05 | 13 | @ | KC | 6-10 | L | 9 | 48 | Arrowhead Stadium |
| 2010-12-12 | 14 | @ |  ARI | 13-43 | L | -4 | 44.5 | University of Phoenix Stadium |
| 2010-12-19 | 15 | @ | OAK | 23-39 | L | 9 | 41.5 | Oakland-Alameda County Coliseum |
| 2010-12-26 | 16 | vs |  HOU | 24-23 | W | -2 | 49.5 | Invesco Field at Mile High |
| 2011-01-02 | 17 | vs | SD | 28-33 | L | -5 | 47.5 | Invesco Field at Mile High |
