| 9/3/2022 | Louisville | 7 | at | Syracuse (7-6,4-4) | 31 | |||
| 9/9/2022 | Louisville | 20 | at | UCF (9-5) | 14 | at AAC | ||
| 9/16/2022 | Florida State (10-3,5-3) | 35 | at | Louisville | 31 | |||
| 9/24/2022 | South Florida (1-11) | 3 | at | Louisville | 41 | AAC | ||
| 10/1/2022 | Louisville | 33 | at | Boston College (3-9,2-6) | 34 | |||
| 10/8/2022 | Louisville | 34 | at | Virginia (3-7,1-6) | 17 | |||
| 10/22/2022 | Pittsburgh (9-4,5-3) | 10 | at | Louisville | 24 | |||
| 10/29/2022 | Wake Forest (8-5,3-5) | 21 | at | Louisville | 48 | |||
| 11/5/2022 | James Madison (8-3) | 10 | at | Louisville | 34 | SBC | ||
| 11/12/2022 | Louisville | 16 | at | Clemson (11-3,9-0) | 31 | |||
| 11/19/2022 | North Carolina State (8-5,4-4) | 10 | at | Louisville | 25 | |||
| 11/26/2022 | Louisville | 13 | at | Kentucky (7-6) | 26 | at SEC | ||
| 12/17/2022 | Cincinnati (9-4) | 7 | vs | Louisville | 24 | Boston MA | AAC |
| vs Louisville | vs Other Opponents | Louisville compared to OOs | |
| Record: | 5-8 | 88-63 | |
| Points Scored: | 19.15 | 29.59 | 10.44 |
| Points Allowed: | 26.92 | 23.97 | 2.95 |
| Margin: | -7.77 | 5.62 | 13.39 |
| Total Points: | 46.07 | 53.56 | -7.49 |