Head Coach: Tom Collen Record: 19-10 (10-6 Big East)
| Date | Site | Opp AP | Opponent | W/L | UL | Opp | Overall | Conf | Attendance | City | State | Arena | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 11/14/2005 | H | Hoosier Lady Stars (Exhibition) | W | 85 | 55 | ||||||||
| 11/20/2005 | H | UC Santa Barbara | W | 76 | 56 | 1-0 | 0-0 | 1,123 | Louisville | Ky. | Freedom Hall | ||
| 11/25/2005 | N | Eastern Kentucky | W | 75 | 45 | 2-0 | 0-0 | Murfreesboro | Tenn. | 2005 MTSU Classic | |||
| 11/26/2005 | N | Georgia Southern | W | 88 | 44 | 3-0 | 0-0 | 440 | Murfreesboro | Tenn. | 2005 MTSU Classic | ||
| 11/29/2005 | A | Western Kentucky | L | 61 | 71 | 3-1 | 0-0 | 2,073 | Bowling Green | Ky. | E.A. Diddle Arena | ||
| 12/04/2005 | H | Indiana | W | 72 | 67 | 4-1 | 0-0 | 1,929 | Louisville | Ky. | Freedom Hall | ||
| 12/10/2005 | H | Xavier | W | 78 | 64 | 5-1 | 0-0 | 1,459 | Louisville | Ky. | Freedom Hall | ||
| 12/15/2005 | H | Northern Colorado | W | 66 | 57 | 6-1 | 0-0 | 976 | Louisville | Ky. | Freedom Hall | ||
| 12/19/2005 | N | Texas Tech | L | 57 | 68 | 6-2 | 0-0 | 230 | Aventura Spa Palace | 2005 Caribbean Classic | |||
| 12/20/2005 | N | Western Michigan | W | 73 | 50 | 7-2 | 0-0 | Aventura Spa Palace | 2005 Caribbean Classic | ||||
| 12/28/2005 | A | Kentucky | W | 64 | 55 | 8-2 | 0-0 | 10,192 | Lexington | Ky. | Rupp Arena | ||
| 12/30/2005 | H | St. Francis | W | 90 | 49 | 9-2 | 0-0 | 1,192 | Louisville | Ky. | Freedom Hall | ||
| 01/03/2006 | A | Syracuse | W | 90 | 73 | 10-2 | 1-0 | 674 | Carrier Dome; Syracuse | N.Y. | |||
| 01/07/2006 | H | Villanova | W | 63 | 57 | 11-2 | 2-0 | 2,309 | Louisville | Ky. | Freedom Hall | ||
| 01/10/2006 | A | West Virginia | L | 73 | 99 | 11-3 | 2-1 | 1,007 | Morgantown | W.Va. | WVU Coliseum | ||
| 01/14/2006 | H | 19 | Notre Dame | W | 61 | 51 | 12-3 | 3-1 | 3,493 | Louisville | Ky. | Freedom Hall | |
| 01/18/2006 | H | Georgetown | W | 89 | 68 | 13-3 | 4-1 | 1,652 | Louisville | Ky. | Freedom Hall | ||
| 01/21/2006 | A | 9 | Rutgers | L | 55 | 80 | 13-4 | 4-2 | 4,759 | Louis Brown Athletic Ctr; Piscataway | N.J. | ||
| 01/25/2006 | A | 10 | DePaul | L | 44 | 48 | 13-5 | 4-3 | 2,645 | DePaul Athletic Center - Chicago | Ill. | ||
| 01/31/2006 | H | 3 | Connecticut | L | 68 | 75 | 13-6 | 4-4 | 9,034 | Louisville | Ky. | Freedom Hall | |
| 02/04/2006 | H | Marquette | W | 70 | 58 | 14-6 | 5-4 | 2,542 | Louisville | Ky. | Freedom Hall | ||
| 02/08/2006 | A | Pittsburgh | W | 71 | 63 | 15-6 | 6-4 | 984 | Pittsburgh | Pa. | Petersen Events Center | ||
| 02/12/2006 | H | Syracuse | W | 64 | 48 | 16-6 | 7-4 | 2,474 | Louisville | Ky. | Freedom Hall | ||
| 02/15/2006 | A | St. John's | L | 63 | 79 | 16-7 | 7-5 | 1,163 | Queens | N.Y. | Carnesecca Arena | ||
| 02/18/2006 | A | Cincinnati | L | 65 | 76 | 16-8 | 7-6 | 712 | Cincinnati | Ohio | Fifth Third Arena | ||
| 02/21/2006 | H | South Florida | W | 65 | 56 | 17-8 | 8-6 | 1,649 | Louisville | Ky. | Freedom Hall | ||
| 02/25/2006 | A | Seton Hall | W | 65 | 45 | 18-8 | 9-6 | 1,355 | South Orange | N.J. | Walsh Gymnasium | ||
| 02/28/2006 | H | Providence | W | 75 | 64 | 19-8 | 10-6 | 2,931 | Louisville | Ky. | Freedom Hall | ||
| 03/04/2006 | N | West Virginia | L | 45 | 54 | 19-9 | 10-6 | 2,006 | Hartford Civic Center Hartford | Conn. | 2006 BIG EAST Tournament | ||
| 03/18/2006 | A | 25 | Vanderbilt | L | 64 | 76 | 19-10 | 10-6 | 4,047 | Nashville | Tenn. | Memorial Gym | 2006 NCAA Tournament First Round |