| 1 | Mon Sep 2 | vs Notre Dame | L17-35 | 0-1 | .000 | Cardinal Stadium · Louisville, KY |
| 2 | Sat Sep 7 | vsE Kentucky | W42-0 | 1-1 | .500 | Cardinal Stadium · Louisville, KY |
| 3 | Sat Sep 14 | atWestern KY | W38-21 | 2-1 | .667 | Houchens Industries-L.T. Smith Stadium · Bowling Green, KY |
| 4 | Sat Sep 21 | atFlorida St | L24-35 | 2-2 | .500 | Doak Campbell Stadium · Tallahassee, FL |
| 5 | Sat Oct 5 | vsBoston College | W41-39 | 3-2 | .600 | Cardinal Stadium · Louisville, KY |
| 6 | Sat Oct 12 | at#19Wake Forest | W62-59 | 4-2 | .667 | Allegacy Federal Credit Union Stadium · Winston-Salem, NC |
| 7 | Sat Oct 19 | vs#3Clemson | L10-45 | 4-3 | .571 | Cardinal Stadium · Louisville, KY |
| 8 | Sat Oct 26 | vsVirginia | W28-21 | 5-3 | .625 | Cardinal Stadium · Louisville, KY |
| 9 | Sat Nov 9 | atMiami | L27-52 | 5-4 | .556 | Hard Rock Stadium · Miami Gardens, FL |
| 10 | Sat Nov 16 | atNC State | W34-20 | 6-4 | .600 | Carter-Finley Stadium · Raleigh, NC |
| 11 | Sat Nov 23 | vsSyracuse | W56-34 | 7-4 | .636 | Cardinal Stadium · Louisville, KY |
| 12 | Sat Nov 30 | atKentucky | L13-45 | 7-5 | .583 | Kroger Field · Lexington, KY |
| BOWLS | Mon Dec 30 | vsMississippi St | W38-28 | 8-5 | .615 | Cardinal Stadium · Louisville, KY |
