12 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | OT | Overall | Conf | Attendance | City | State | Stadium | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 09/04/2005 | A | Kentucky | 12 | W | 31 | 24 | 1-0 | 70,752 | Lexington | Ky. | Commonwealth Stadium | ||||
| 09/17/2005 | H | RV | Oregon State | 11 | W | 63 | 27 | 2-0 | 42,647 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 09/24/2005 | A | South Florida | 9 | L | 14 | 45 | 2-1 | 0-1 | 33,586 | Tampa | Fla. | Raymond James Stadium | |||
| 10/01/2005 | H | Florida Atlantic | 24 | W | 61 | 10 | 3-1 | 0-1 | 40,219 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 10/08/2005 | H | RV | North Carolina | 23 | W | 69 | 14 | 4-1 | 0-1 | 41,334 | Louisville | Ky. | Papa John's Cardinal Stadium | ||
| 10/15/2005 | A | RV | West Virginia | 19 | L | 44 | 46 | 3 OT | 4-2 | 0-2 | 59,797 | Morgantown | W.Va. | Milan Puskar Stadium | |
| 10/22/2005 | A | Cincinnati | RV | W | 46 | 22 | 5-2 | 1-2 | 21,086 | Cincinnati | Ohio | Nippert Stadium | |||
| 11/03/2005 | H | Pittsburgh | 24 | W | 42 | 20 | 6-2 | 2-2 | 42,692 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 11/11/2005 | H | Rutgers | 23 | W | 56 | 5 | 7-2 | 3-2 | 41,219 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 11/26/2005 | H | Syracuse | 17 | W | 41 | 17 | 8-2 | 4-2 | 37,896 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 12/03/2005 | A | Connecticut | 16 | W | 30 | 20 | 9-2 | 5-2 | 40,000 | East Hartford | Conn. | Rentschler Field | |||
| 01/02/2006 | N | 12 | Virginia Tech | 15 | L | 24 | 35 | 9-3 | 5-2 | 63,780 | Jacksonville | Fla. | Alltel Stadium | Gator Bowl |