13 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | OT | Overall | Conf | Attendance | City | State | Stadium | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 09/03/2022 | A | Syracuse | L | 7 | 31 | 0-1 | 0-1 | 37,110 | Syracuse | N.Y. | JMA Wireless Dome | ||||
| 09/09/2022 | A | Central Florida | W | 20 | 14 | 1-1 | 0-1 | 44,412 | Orlando | Fla. | FBC Mortgage Stadium | ||||
| 09/16/2022 | H | Florida State | L | 31 | 35 | 1-2 | 0-2 | 46,459 | Louisville | Ky. | Cardinal Stadium | ||||
| 09/24/2022 | H | South Florida | W | 41 | 3 | 2-2 | 0-2 | 41,217 | Louisville | Ky. | Cardinal Stadium | ||||
| 10/01/2022 | A | Boston College | L | 33 | 34 | 2-3 | 0-3 | 38,517 | Chestnut Hill | Mass. | Alumni Stadium | ||||
| 10/08/2022 | A | Virginia | W | 34 | 17 | 3-3 | 1-3 | 38,009 | Charlottesville | Va. | Scott Stadium | ||||
| 10/22/2022 | H | Pittsburgh | W | 24 | 10 | 4-3 | 2-3 | 41,840 | Louisville | Ky. | Cardinal Stadium | ||||
| 10/29/2022 | H | 10 | Wake Forest | W | 48 | 21 | 5-3 | 3-3 | 39,503 | Louisville | Ky. | Cardinal Stadium | |||
| 11/05/2022 | H | James Madison | W | 34 | 10 | 6-3 | 3-3 | 42,157 | Louisville | Ky. | Cardinal Stadium | ||||
| 11/12/2022 | A | 12 | Clemson | L | 16 | 31 | 6-4 | 3-4 | 80,176 | Clemson | S.C. | Memorial Stadium | |||
| 11/19/2022 | H | North Carolina State | W | 25 | 10 | 7-4 | 4-4 | 38,974 | Louisville | Ky. | Cardinal Stadium | ||||
| 11/26/2022 | A | Kentucky | L | 13 | 26 | 7-5 | 4-4 | 58,727 | Lexington | Ky. | Kroger Field | ||||
| 12/17/2022 | N | Cincinnati | W | 24 | 7 | 8-5 | 4-4 | 15,000 | Boston | Mass. | Fenway Park | Wasabi Fenway Bowl |