12 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | OT | Overall | Conf | Attendance | City | State | Stadium | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 08/31/2008 | H | Kentucky | L | 2 | 27 | 0-1 | 42,696 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 09/06/2008 | H | Tennessee Tech | W | 51 | 10 | 1-1 | 38,694 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 09/17/2008 | H | Kansas State | W | 38 | 29 | 2-1 | 42,208 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 09/26/2008 | H | RV | Connecticut | L | 21 | 26 | 2-2 | 0-1 | 42,523 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 10/10/2008 | A | Memphis | W | 35 | 28 | 3-2 | 0-1 | 40,248 | Memphis | Tenn. | Liberty Bowl Memorial Stadium | ||||
| 10/18/2008 | H | Middle Tennessee | W | 42 | 23 | 4-2 | 0-1 | 38,319 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 10/25/2008 | H | 14 | South Florida | W | 24 | 20 | 5-2 | 1-1 | 40,384 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 11/01/2008 | A | Syracuse | RV | L | 21 | 28 | 5-3 | 1-2 | 32,917 | Syracuse | N.Y. | Carrier Dome | |||
| 11/08/2008 | A | 25 | Pittsburgh | RV | L | 7 | 41 | 5-4 | 1-3 | 44,055 | Pittsburgh | Pa. | Heinz Field | ||
| 11/14/2008 | H | 22 | Cincinnati | L | 20 | 28 | 5-5 | 1-4 | 37,822 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 11/22/2008 | H | RV | West Virginia | L | 21 | 35 | 5-6 | 1-5 | 34,796 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 12/04/2008 | A | Rutgers | L | 14 | 63 | 5-7 | 1-6 | 42,347 | Piscataway | N.J. | Rutgers Stadium |