| Rk | Day | Date | Tm | Opp | Tm | Opp | |||
|---|---|---|---|---|---|---|---|---|---|
| 1 | Sun | September 7, 2008 | W | Buffalo Bills | Seattle Seahawks | 34 | 10 | box | |
| 2 | Sun | September 14, 2008 | W | Buffalo Bills | @ | Jacksonville Jaguars | 20 | 16 | box |
| 3 | Sun | September 21, 2008 | W | Buffalo Bills | Oakland Raiders | 24 | 23 | box | |
| 4 | Sun | September 28, 2008 | W | Buffalo Bills | @ | St. Louis Rams | 31 | 14 | box |
| 5 | Sun | October 5, 2008 | L | Buffalo Bills | @ | Arizona Cardinals | 17 | 41 | box |
| 6 | Sun | October 19, 2008 | W | Buffalo Bills | San Diego Chargers | 23 | 14 | box | |
| 7 | Sun | October 26, 2008 | L | Buffalo Bills | @ | Miami Dolphins | 16 | 25 | box |
| 8 | Sun | November 2, 2008 | L | Buffalo Bills | New York Jets | 17 | 26 | box | |
| 9 | Sun | November 9, 2008 | L | Buffalo Bills | @ | New England Patriots | 10 | 20 | box |
| 10 | Mon | November 17, 2008 | L | Buffalo Bills | Cleveland Browns | 27 | 29 | box | |
| 11 | Sun | November 23, 2008 | W | Buffalo Bills | @ | Kansas City Chiefs | 54 | 31 | box |
| 12 | Sun | November 30, 2008 | L | Buffalo Bills | San Francisco 49ers | 3 | 10 | box | |
| 13 | Sun | December 21, 2008 | W | Buffalo Bills | @ | Denver Broncos | 30 | 23 | box |
| 14 | Sun | December 28, 2008 | L | Buffalo Bills | New England Patriots | 0 | 13 | box |