Schedule:
Please note: All rankings shown are the rankings of the teams on the date that they played one another
| Game | Date | Away Team (Rank) | Away Score | Home Score | Home Team (Rank) | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-10-29 | Kentucky State | 45 | 94 | Louisville (50) | Final | W | 49 |
| 2 | 2021-11-03 | West Georgia | 51 | 103 | Louisville (50) | Final | W | 52 |
| 3 | 2021-11-09 | Southern (287) | 60 | 72 | Louisville (50) | Final | W | 12 |
| 4 | 2021-11-12 | Furman (157) | 80 | 72 | Louisville (21) | Final/OT | L | -8 |
| 5 | 2021-11-15 | Navy (144) | 60 | 77 | Louisville (140) | Final | W | 17 |
| 6 | 2021-11-20 | Detroit (212) | 67 | 73 | Louisville (21) | Final | W | 6 |
| 7 | 2021-11-25 | Mississippi State (100) | 58 | 72 | Louisville (21) | Final | W | 14 |
| 8 | 2021-11-27 | Louisville (120) | 63 | 55 | Maryland (61) | Final | W | 8 |
| 9 | 2021-12-01 | Louisville (21) | 64 | 73 | Michigan State (10) | Final | L | -9 |
| 10 | 2021-12-04 | Louisville (21) | 73 | 68 | North Carolina State (44) | Final | W | 5 |
| 11 | 2021-12-10 | DePaul (54) | 62 | 55 | Louisville (48) | Final | L | -7 |
| 12 | 2021-12-14 | Southeastern Louisiana (318) | 60 | 86 | Louisville (21) | Final | W | 26 |
| 13 | 2021-12-18 | Louisville (21) | 72 | 82 | Western Kentucky (154) | Final | L | -10 |
| 14 | 2021-12-22 | Louisville (71) | 0 | 0 | Kentucky (40) | Cancelled | - | - |
| 15 | 2021-12-29 | Wake Forest (70) | 69 | 73 | Louisville (21) | Final | W | 4 |
| 16 | 2022-01-02 | Louisville (21) | 67 | 64 | Georgia Tech (158) | Final | W | 3 |
| 17 | 2022-01-05 | Pittsburgh (108) | 72 | 75 | Louisville (21) | Final | W | 3 |
| 18 | 2022-01-08 | Louisville (21) | 70 | 79 | Florida State (64) | Final | L | -9 |
| 19 | 2022-01-12 | North Carolina State (135) | 79 | 63 | Louisville (65) | Final | L | -16 |
| 20 | 2022-01-15 | Louisville (21) | 53 | 65 | Pittsburgh (108) | Final | L | -12 |
| 21 | 2022-01-19 | Boston College (151) | 54 | 67 | Louisville (21) | Final | W | 13 |
| 22 | 2022-01-22 | Notre Dame (101) | 82 | 70 | Louisville (21) | Final | L | -12 |
| 23 | 2022-01-24 | Louisville (21) | 52 | 64 | Virginia (14) | Final | L | -12 |
| 24 | 2022-01-29 | Duke (3) | 74 | 65 | Louisville (21) | Final | L | -9 |
| 25 | 2022-02-01 | North Carolina (45) | 90 | 83 | Louisville (112) | Final (OT) | L | -7 |
| 26 | 2022-02-05 | Louisville (21) | 69 | 92 | Syracuse (84) | Final | L | -23 |
| 27 | 2022-02-09 | Louisville (21) | 57 | 63 | Notre Dame (101) | Final | L | -6 |
| 28 | 2022-02-16 | Miami (43) | 70 | 63 | Louisville (121) | Final | L | -7 |
| 29 | 2022-02-19 | Clemson (102) | 61 | 70 | Louisville (121) | Final | W | 9 |
| 30 | 2022-02-21 | Louisville (117) | 63 | 70 | North Carolina (39) | Final | L | -7 |
| 31 | 2022-02-26 | Louisville (117) | 77 | 99 | Wake Forest (37) | Final | L | -22 |
| 32 | 2022-03-01 | Louisville (121) | 43 | 75 | Virginia Tech (60) | Final | L | -32 |
| 33 | 2022-03-05 | Virginia (80) | 71 | 61 | Louisville (121) | Final | L | -10 |
| 34 | 2022-03-08 | Georgia Tech (165) | 74 | 84 | Louisville (128) | Final | W | 10 |
| 35 | 2022-03-09 | Louisville (128) | 50 | 51 | Virginia (77) | Final | L | -1 |