| 2008-09-07 | 1 | @ |  SF | 23-13 | W | -2.5 | 42 | Candlestick Park |
| 2008-09-14 | 2 | vs |  MIA | 31-10 | W | 6.5 | 40.5 | University of Phoenix Stadium |
| 2008-09-21 | 3 | @ |  WAS | 17-24 | L | 3 | 43.5 | FedExField |
| 2008-09-28 | 4 | @ |  NYJ | 35-56 | L | 1.5 | 43.5 | Giants Stadium |
| 2008-10-05 | 5 | vs |  BUF | 41-17 | W | 1 | 44.5 | University of Phoenix Stadium |
| 2008-10-12 | 6 | vs |  DAL | 30-24 | W | -4.5 | 53 | University of Phoenix Stadium |
| 2008-10-26 | 8 | @ |  CAR | 23-27 | L | 5 | 43 | Bank of America Stadium |
| 2008-11-02 | 9 | @ |  STL | 34-13 | W | -3 | 49.5 | Edward Jones Dome |
| 2008-11-10 | 10 | vs | SF | 29-24 | W | 9.5 | 47.5 | University of Phoenix Stadium |
| 2008-11-16 | 11 | @ |  SEA | 26-20 | W | -3 | 47.5 | Qwest Field |
| 2008-11-23 | 12 | vs |  NYG | 29-37 | L | -3 | 48 | University of Phoenix Stadium |
| 2008-11-27 | 13 | @ |  PHI | 20-48 | L | 3 | 48.5 | Lincoln Financial Field |
| 2008-12-07 | 14 | vs | STL | 34-10 | W | 14 | 48.5 | University of Phoenix Stadium |
| 2008-12-14 | 15 | vs |  MIN | 14-35 | L | 4 | 46.5 | University of Phoenix Stadium |
| 2008-12-21 | 16 | @ |  NE | 7-47 | L | 9 | 41 | Gillette Stadium |
| 2008-12-28 | 17 | vs | SEA | 34-21 | W | 7 | 47 | University of Phoenix Stadium |
| 2009-01-03 | 18 | vs |  ATL | 30-24 | W | 2 | 52 | University of Phoenix Stadium |
| 2009-01-10 | 19 | @ | CAR | 33-13 | W | 10 | 49.5 | Bank of America Stadium |
| 2009-01-18 | 20 | vs | PHI | 32-25 | W | -3.5 | 47 | University of Phoenix Stadium |
| 2009-02-01 | 21 | vs |  PIT | 23-27 | L | -6.5 | 46.5 | Raymond James Stadium |
