32 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | OT | Overall | Conf | Attendance | City | State | Arena | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 11/09/2021 | H | Southern | W | 72 | 60 | 1-0 | 12,643 | Louisville | Ky. | KFC Yum! Center | |||||
| 11/12/2021 | H | Furman | L | 72 | 80 | OT | 1-1 | 12,431 | Louisville | Ky. | KFC Yum! Center | ||||
| 11/15/2021 | H | Navy | W | 77 | 60 | 2-1 | 12,223 | Louisville | Ky. | KFC Yum! Center | |||||
| 11/20/2021 | H | Detroit Mercy | W | 73 | 67 | 3-1 | 12,561 | Louisville | Ky. | KFC Yum! Center | 2021 Baha Mar Hoops Bahamas Championship | ||||
| 11/25/2021 | N | Mississippi State | W | 72 | 58 | 4-1 | 1,249 | Nassau | Bahamas | Baha Mar Convention Center | 2021 Baha Mar Hoops Bahamas Championship | ||||
| 11/27/2021 | N | Maryland | W | 63 | 55 | 5-1 | 1,175 | Nassau | Bahamas | Baha Mar Convention Center | 2021 Baha Mar Hoops Bahamas Championship | ||||
| 12/01/2021 | A | 22 | Michigan State | L | 64 | 73 | 5-2 | 14,797 | East Lansing | Mich. | Breslin Center | ||||
| 12/04/2021 | A | North Carolina State | W | 73 | 68 | 6-2 | 1-0 | 13,029 | Raleigh | N.C. | PNC Arena | ||||
| 12/10/2021 | H | DePaul | L | 55 | 62 | 6-3 | 1-0 | 13,127 | Louisville | Ky. | KFC Yum! Center | ||||
| 12/14/2021 | H | Southeastern Louisiana | W | 86 | 60 | 7-3 | 1-0 | 12,247 | Louisville | Ky. | KFC Yum! Center | ||||
| 12/18/2021 | A | Western Kentucky | L | 72 | 82 | 7-4 | 1-0 | 7,053 | Bowling Green | Ky. | Diddle Arena | ||||
| 12/29/2021 | H | Wake Forest | W | 73 | 69 | 8-4 | 2-0 | 14,120 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/02/2022 | A | Georgia Tech | W | 67 | 64 | 9-4 | 3-0 | 4,853 | Atlanta | Ga. | McCamish Pavilion | ||||
| 01/05/2022 | H | Pittsburgh | W | 75 | 72 | 10-4 | 4-0 | 11,973 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/08/2022 | A | Florida State | L | 70 | 79 | 10-5 | 4-1 | 9,527 | Tallahassee | Fla. | Donald L. Tucker Civic Center | ||||
| 01/12/2022 | H | North Carolina State | L | 63 | 79 | 10-6 | 4-2 | 11,973 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/15/2022 | A | Pittsburgh | L | 53 | 65 | 10-7 | 4-3 | 8,431 | Pittsburgh | Pa. | Petersen Events Center | ||||
| 01/19/2022 | H | Boston College | W | 67 | 54 | 11-7 | 5-3 | 12,123 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/22/2022 | H | Notre Dame | L | 70 | 82 | 11-8 | 5-4 | 16,175 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/24/2022 | A | Virginia | L | 52 | 64 | 11-9 | 5-5 | 13,076 | Charlottesville | Va. | John Paul Jones Arena | ||||
| 01/29/2022 | H | 9 | Duke | L | 65 | 74 | 11-10 | 5-6 | 18,493 | Louisville | Ky. | KFC Yum! Center | |||
| 02/01/2022 | H | North Carolina | L | 83 | 90 | OT | 11-11 | 5-7 | 13,386 | Louisville | Ky. | KFC Yum! Center | |||
| 02/05/2022 | A | Syracuse | L | 69 | 92 | 11-12 | 5-8 | 23,298 | Syracuse | N.Y. | Carrier Dome | ||||
| 02/09/2022 | A | Notre Dame | L | 57 | 63 | 11-13 | 5-9 | 8,260 | South Bend | Ind. | Purcell Pavillion at Joyce Center | ||||
| 02/16/2022 | H | Miami, Fla. | L | 63 | 70 | 11-14 | 5-10 | 12,065 | Louisville | Ky. | KFC Yum! Center | ||||
| 02/19/2022 | H | Clemson | W | 70 | 61 | 12-14 | 6-10 | 13,242 | Louisville | Ky. | KFC Yum! Center | ||||
| 02/21/2022 | A | North Carolina | L | 63 | 70 | 12-15 | 6-11 | 18,618 | Chapel Hill | N.C. | Dean E. Smith Center | ||||
| 02/26/2022 | A | Wake Forest | L | 77 | 99 | 12-16 | 6-12 | 8,139 | Winston-Salem | N.C. | Lawrence Joel Veterans Memorial Coliseum | ||||
| 03/01/2022 | A | Virginia Tech | L | 43 | 75 | 12-17 | 6-13 | 8,925 | Blacksburg | Va. | Cassell Coliseum | ||||
| 03/05/2022 | H | Virginia | L | 61 | 71 | 12-18 | 6-14 | 13,085 | Louisville | Ky. | KFC Yum! Center | ||||
| 03/08/2022 | N | Georgia Tech | W | 84 | 74 | 13-18 | 6-14 | 6,222 | Brooklyn | N.Y. | Barclays Center | 2022 New York Life ACC Men's Basketball Tournament First Round | |||
| 03/09/2022 | N | Virginia | L | 50 | 51 | 13-19 | 6-14 | 8,174 | Brooklyn | N.Y. | Barclays Center | 2022 New York Life ACC Men's Basketball Tournament Second Round |