30 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | Overall | Conf | Attendance | City | State | Arena | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1980-11-22 | N | 2 | DePaul | 3 | L | 80 | 86 | 0-1 | 0-0 | 8,937 | Springfield | MA | Springfield Civic Center | 1980 Hall of Fame Game |
| 1980-12-04 | A | Tulsa | 8 | L | 60 | 68 | 0-2 | 0-0 | 8,617 | Tulsa | OK | Tulsa Assembly Center | ||
| 1980-12-06 | A | Oklahoma State | 8 | L | 71 | 72 | 0-3 | 0-0 | 6,600 | Stillwater | OK | Gallagher-Iba Arena | ||
| 1980-12-13 | H | 4 | Maryland | W | 78 | 67 | 1-3 | 0-0 | 15,072 | Louisville | KY | Freedom Hall | ||
| 1980-12-20 | H | Utah | 20 | L | 59 | 78 | 1-4 | 0-0 | 16,613 | Louisville | KY | Freedom Hall | ||
| 1980-12-22 | H | Minnesota | L | 56 | 62 | 1-5 | 0-0 | 13,856 | Louisville | KY | Freedom Hall | |||
| 1980-12-29 | N | 6 | North Carolina | L | 64 | 86 | 1-6 | 0-0 | 6,000 | Los Angeles | CA | L.A. Sports Arena | 1980 Winston Tire Basketball Classic | |
| 1980-12-30 | N | Southern California | W | 79 | 50 | 2-6 | 0-0 | 5,032 | Los Angeles | CA | L.A. Sports Arena | 1980 Winston Tire Basketball Classic | ||
| 1981-01-03 | A | Kansas State | L | 47 | 64 | 2-7 | 0-0 | 11,220 | Manhattan | KS | Ahearn Field House | |||
| 1981-01-05 | A | Tulane | W | 73 | 53 | 3-7 | 1-0 | 3,153 | New Orleans | LA | Superdome | |||
| 1981-01-10 | A | Cincinnati | W | 83 | 68 | 4-7 | 2-0 | 10,000 | Cincinnati | OH | Riverfront Coliseum | |||
| 1981-01-17 | H | Florida State | W | 98 | 78 | 5-7 | 3-0 | 16,613 | Louisville | KY | Freedom Hall | |||
| 1981-01-18 | H | Missouri | W | 71 | 49 | 6-7 | 3-0 | 13,386 | Louisville | KY | Freedom Hall | |||
| 1981-01-22 | A | Memphis | L | 55 | 60 | 6-8 | 3-1 | 11,200 | Memphis | TN | Mid-South Coliseum | |||
| 1981-01-27 | H | Providence | W | 71 | 55 | 7-8 | 3-1 | 14,382 | Louisville | KY | Freedom Hall | |||
| 1981-01-29 | H | Saint Louis | W | 61 | 57 | 8-8 | 4-1 | 15,127 | Louisville | KY | Freedom Hall | |||
| 1981-01-31 | H | Virginia Tech | W | 92 | 70 | 9-8 | 5-1 | 15,428 | Louisville | KY | Freedom Hall | |||
| 1981-02-02 | H | US International | W | 86 | 68 | 10-8 | 5-1 | 13,331 | Louisville | KY | Freedom Hall | |||
| 1981-02-04 | H | Tulane | W | 85 | 58 | 11-8 | 6-1 | 14,836 | Louisville | KY | Freedom Hall | |||
| 1981-02-07 | A | Florida State | W | 82 | 73 | 12-8 | 7-1 | 2,982 | Tallahassee | FL | Tully Gymnasium | |||
| 1981-02-09 | A | Virginia Tech | W | 71 | 66 | 13-8 | 8-1 | 8,800 | Blacksburg | VA | Cassell Coliseum | |||
| 1981-02-14 | A | Marquette | W | 79 | 60 | 14-8 | 8-1 | 11,052 | Milwaukee | WI | Milwaukee Arena | |||
| 1981-02-16 | H | Memphis | W | 95 | 65 | 15-8 | 9-1 | 16,613 | Louisville | KY | Freedom Hall | |||
| 1981-02-18 | H | Iona | W | 91 | 57 | 16-8 | 9-1 | 16,613 | Louisville | KY | Freedom Hall | |||
| 1981-02-23 | H | Cincinnati | 20 | W | 81 | 67 | 17-8 | 10-1 | 16,426 | Louisville | KY | Freedom Hall | ||
| 1981-02-25 | A | Saint Louis | 20 | W | 97 | 85 | 18-8 | 11-1 | 5,131 | St. Louis | MO | Checkerdome | ||
| 1981-02-28 | H | Western Kentucky | 20 | W | 90 | 75 | 19-8 | 11-1 | 16,613 | Louisville | KY | Freedom Hall | ||
| 1981-03-06 | H | Virginia Tech | 17 | W | 81 | 68 | 20-8 | 11-1 | 12,441 | Louisville | KY | Freedom Hall | 1981 Metro Tournament Semifinal | |
| 1981-03-07 | H | Cincinnati | 17 | W | 42 | 31 | 21-8 | 11-1 | 11,192 | Louisville | KY | Freedom Hall | 1981 Metro Tournament Final | |
| 1981-03-14 | N | 20 | Arkansas | 12 | L | 73 | 74 | 21-9 | 11-1 | 8,523 | Austin | TX | Erwin Center | 1981 NCAA Tournament Second Round |