| Rk | Gcar | Gtm | Date | School | Opponent | Type | Result | Bowl | |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 1 | 1 | 2021-09-06 | Louisville | N | Ole Miss | REG (Non-Conf) | L 24-43 | |
| 2 | 2 | 3 | 2021-09-17 | Louisville | UCF | REG (Non-Conf) | W 42-35 | ||
| 3 | 3 | 4 | 2021-09-25 | Louisville | @ | Florida State | REG (Conf) | W 31-23 | |
| 4 | 4 | 5 | 2021-10-02 | Louisville | @ | Wake Forest | REG (Conf) | L 34-37 | |
| 5 | 5 | 6 | 2021-10-09 | Louisville | Virginia | REG (Conf) | L 33-34 | ||
| 6 | 6 | 7 | 2021-10-23 | Louisville | Boston College | REG (Conf) | W 28-14 | ||
| 7 | 7 | 8 | 2021-10-30 | Louisville | @ | North Carolina State | REG (Conf) | L 13-28 | |
| 8 | 8 | 9 | 2021-11-06 | Louisville | Clemson | REG (Conf) | L 24-30 | ||
| 9 | 9 | 10 | 2021-11-13 | Louisville | Syracuse | REG (Conf) | W 41-3 | ||
| 10 | 10 | 12 | 2021-11-27 | Louisville | Kentucky | REG (Non-Conf) | L 21-52 | ||
| 11 | 11 | 13 | 2021-12-28 | Louisville | N | Air Force | Bowl | L 28-31 | First Responder Bowl |
| 4-7 |
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