13 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | OT | Overall | Conf | Attendance | City | State | Stadium | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 09/04/2010 | H | Kentucky | L | 16 | 23 | 0-1 | 55,327 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 09/11/2010 | H | Eastern Kentucky | W | 23 | 13 | 1-1 | 51,427 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 09/18/2010 | A | 25 | Oregon State | L | 28 | 35 | 1-2 | 45,379 | Corvallis | Ore. | Reser Stadium | ||||
| 10/02/2010 | A | Arkansas State | W | 34 | 24 | 2-2 | 25,219 | Jonesboro | Ark. | ASU Stadium | |||||
| 10/09/2010 | H | Memphis | W | 56 | 0 | 3-2 | 48,427 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 10/15/2010 | H | Cincinnati | L | 27 | 35 | 3-3 | 0-1 | 55,106 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 10/23/2010 | H | Connecticut | W | 26 | 0 | 4-3 | 1-1 | 48,591 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 10/30/2010 | A | Pittsburgh | L | 3 | 20 | 4-4 | 1-2 | 48,562 | Pittsburgh | Pa. | Heinz Field | ||||
| 11/06/2010 | A | Syracuse | W | 28 | 20 | 5-4 | 2-2 | 40,735 | Syracuse | N.Y. | Carrier Dome | ||||
| 11/13/2010 | H | South Florida | L | 21 | 24 | OT | 5-5 | 2-3 | 43,887 | Louisville | Ky. | Papa John's Cardinal Stadium | |||
| 11/20/2010 | H | West Virginia | L | 10 | 17 | 5-6 | 2-4 | 51,772 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 11/26/2010 | A | Rutgers | W | 40 | 13 | 6-6 | 3-4 | 37,422 | Piscataway | N.J. | Rutgers Stadium | ||||
| 12/21/2010 | N | Southern Mississippi | W | 31 | 28 | 7-6 | 3-4 | 20,017 | St. Petersburg | Fla. | Tropicana Field | Beef 'O' Brady's Bowl |