12 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | OT | Overall | Conf | Attendance | City | State | Stadium | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 09/02/2000 | H | Kentucky | W | 40 | 34 | OT | 1-0 | 42,510 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 09/09/2000 | H | Grambling | W | 52 | 0 | 2-0 | 41,227 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 09/23/2000 | A | 2 | Florida State | L | 0 | 31 | 2-1 | 80,741 | Tallahassee | Fla. | Doak Campbell Stadium | ||||
| 09/30/2000 | H | Connecticut | W | 41 | 22 | 3-1 | 38,121 | Louisville | Ky. | Papa John's Cardinal Stadium | |||||
| 10/07/2000 | A | Alabama-Birmingham | W | 38 | 17 | 4-1 | 1-0 | 18,000 | Birmingham | Ala. | |||||
| 10/14/2000 | H | Cincinnati | W | 38 | 24 | 5-1 | 2-0 | 39,233 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 10/19/2000 | H | East Carolina | L | 25 | 28 | 5-2 | 2-1 | 38,024 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 10/28/2000 | H | Tulane | W | 35 | 32 | 6-2 | 3-1 | 30,387 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 11/04/2000 | A | 13 | Southern Mississippi | W | 49 | 28 | 7-2 | 4-1 | 31,667 | Hattiesburg | Miss. | ||||
| 11/11/2000 | H | Army | W | 38 | 17 | 8-2 | 5-1 | 40,328 | Louisville | Ky. | Papa John's Cardinal Stadium | ||||
| 11/18/2000 | A | Houston | W | 32 | 13 | 9-2 | 6-1 | 3,006 | Houston | Texas | Robertson Stadium | ||||
| 12/29/2000 | N | 23 | Colorado State | 22 | L | 17 | 22 | 9-3 | 6-1 | 58,302 | Memphis | Tenn. | Liberty Bowl Memorial Stadium | Liberty Bowl |