| 2010-09-12 | 1 | @ |  TEN | 13-38 | L | 6.5 | 39.5 | LP Field |
| 2010-09-19 | 2 | vs |  STL | 16-14 | W | 3 | 37.5 | Oakland-Alameda County Coliseum |
| 2010-09-26 | 3 | @ |  ARI | 23-24 | L | 5.5 | 38.5 | University of Phoenix Stadium |
| 2010-10-03 | 4 | vs |  HOU | 24-31 | L | -3.5 | 43.5 | Oakland-Alameda County Coliseum |
| 2010-10-10 | 5 | vs |  SD | 35-27 | W | -7 | 44 | Oakland-Alameda County Coliseum |
| 2010-10-17 | 6 | @ |  SF | 9-17 | L | 9 | 40.5 | Candlestick Park |
| 2010-10-24 | 7 | @ |  DEN | 59-14 | W | 7 | 43 | Invesco Field at Mile High |
| 2010-10-31 | 8 | vs |  SEA | 33-3 | W | 1.5 | 39.5 | Oakland-Alameda County Coliseum |
| 2010-11-07 | 9 | vs |  KC | 23-20 | W | -1 | 41 | Oakland-Alameda County Coliseum |
| 2010-11-21 | 11 | @ |  PIT | 3-35 | L | 7 | 41 | Heinz Field |
| 2010-11-28 | 12 | vs |  MIA | 17-33 | L | 3 | 38 | Oakland-Alameda County Coliseum |
| 2010-12-05 | 13 | @ | SD | 28-13 | W | 12.5 | 44.5 | Qualcomm Stadium |
| 2010-12-12 | 14 | @ |  JAX | 31-38 | L | 3.5 | 41 | EverBank Field |
| 2010-12-19 | 15 | vs | DEN | 39-23 | W | 9 | 41.5 | Oakland-Alameda County Coliseum |
| 2010-12-26 | 16 | vs |  IND | 26-31 | L | -1 | 46 | Oakland-Alameda County Coliseum |
| 2011-01-02 | 17 | @ | KC | 31-10 | W | 4.5 | 43 | Arrowhead Stadium |
