Head Coach: Dani Busboom Kelly Record: 32-1 (18-0 ACC)
| Date | Site | Opp Rk | Opponent | W/L | UL | Opp | Overall | Conf | Attendance | City | Arena | Event | Type |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 08/27/2021 | N | Cal Poly | W | 3 | 0 | 1-0 | 0-0 | 147 | Tempe, Ariz. | Desert Financial Arena | Arizona State Tournament | ||
| 08/27/2021 | N | Texas A&M-Corpus Christi | W | 3 | 0 | 2-0 | 0-0 | 147 | Tempe, Ariz. | Desert Financial Arena | |||
| 08/28/2021 | A | Arizona State | W | 3 | 2 | 3-0 | 0-0 | 1,073 | Tempe, Ariz. | Desert Financial Arena | |||
| 09/03/2021 | H | Missouri | W | 3 | 0 | 4-0 | 0-0 | 867 | Louisville, Ky. | L&N Federal Credit Union Arena | Cardinal Classic | ||
| 09/04/2021 | H | South Dakota | W | 3 | 0 | 5-0 | 0-0 | 897 | Louisville, Ky. | L&N Federal Credit Union Arena | Cardinal Classic | ||
| 09/05/2021 | H | Northern Kentucky | W | 3 | 0 | 6-0 | 0-0 | 987 | Louisville, Ky. | L&N Federal Credit Union Arena | Cardinal Classic | ||
| 09/10/2021 | N | 6 | Purdue | W | 3 | 0 | 7-0 | 0-0 | Cincinnati, Ohio | Cintas Center | |||
| 09/11/2021 | A | Xavier | W | 3 | 0 | 8-0 | 0-0 | 420 | Cincinnati, Ohio | Cintas Center | |||
| 09/15/2021 | H | 8 | Kentucky | W | 3 | 2 | 9-0 | 0-0 | 1,258 | Louisville, Ky. | L&N Federal Credit Union Arena | ||
| 09/18/2021 | A | 6 | Nebraska | W | 3 | 0 | 10-0 | 0-0 | 8,286 | Lincoln, Neb. | Bob Devaney Sports Center | ||
| 09/24/2021 | H | Miami, Fla. | W | 3 | 0 | 11-0 | 1-0 | 958 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | ||
| 09/26/2021 | H | Florida State | W | 3 | 0 | 12-0 | 2-0 | 903 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | ||
| 10/01/2021 | A | Clemson | W | 3 | 0 | 13-0 | 3-0 | 678 | Clemson, S.C. | Jervey Gymnasium | Conf | ||
| 10/03/2021 | A | 18 | Georgia Tech | W | 3 | 0 | 14-0 | 4-0 | 1,200 | Atlanta, Ga. | O'Keefe Gym | Conf | |
| 10/08/2021 | H | Boston College | W | 3 | 0 | 15-0 | 5-0 | 1,041 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | ||
| 10/10/2021 | H | Syracuse | W | 3 | 0 | 16-0 | 6-0 | 988 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | ||
| 10/15/2021 | A | Virginia Tech | W | 3 | 0 | 17-0 | 7-0 | 473 | Blacksburg, Va. | Cassell Coliseum | Conf | ||
| 10/17/2021 | A | Wake Forest | W | 3 | 1 | 18-0 | 8-0 | 260 | Winston-Salem, N.C. | Reynolds Gym | Conf | ||
| 10/22/2021 | H | Virginia | W | 3 | 0 | 19-0 | 9-0 | 1,098 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | ||
| 10/24/2021 | H | 4 | Pittsburgh | W | 3 | 2 | 20-0 | 10-0 | 1,198 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | |
| 10/31/2021 | A | Duke | W | 3 | 1 | 21-0 | 11-0 | 727 | Durham, N.C. | Cameron Indoor Stadium | Conf | ||
| 11/05/2021 | A | North Carolina State | W | 3 | 0 | 22-0 | 12-0 | 1,605 | Raleigh, N.C. | Reynolds Coliseum | Conf | ||
| 11/07/2021 | A | North Carolina | W | 3 | 1 | 23-0 | 13-0 | 1,496 | Chapel Hill, N.C. | Carmichael Arena | Conf | ||
| 11/12/2021 | H | 14 | Georgia Tech | W | 3 | 0 | 24-0 | 14-0 | 1,100 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | |
| 11/15/2021 | A | Notre Dame | W | 3 | 0 | 25-0 | 15-0 | 351 | South Bend, Ind. | Purcell Pavilion at the Joyce Center | Conf | ||
| 11/19/2021 | H | Duke | W | 3 | 0 | 26-0 | 16-0 | 1,098 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | ||
| 11/24/2021 | A | 3 | Pittsburgh | W | 3 | 1 | 27-0 | 17-0 | 3,052 | Pittsburgh, Pa. | Fitzgerald Field House | Conf | |
| 11/26/2021 | H | Notre Dame | W | 3 | 1 | 28-0 | 18-0 | 1,067 | Louisville, Ky. | L&N Federal Credit Union Arena | Conf | ||
| 12/03/2021 | H | Illinois-Chicago | W | 3 | 0 | 29-0 | 18-0 | 993 | Louisville, Ky. | L&N Federal Credit Union Arena | NCAA Volleyball Championship | NCAA 1st Round | |
| 12/04/2021 | H | Ball State | W | 3 | 0 | 30-0 | 18-0 | 1,055 | Louisville, Ky. | L&N Federal Credit Union Arena | NCAA Volleyball Championship | NCAA 2nd Round | |
| 12/09/2021 | H | 16 | Florida | W | 3 | 0 | 31-0 | 18-0 | 3,089 | Louisville, Ky. | Freedom Hall | NCAA Volleyball Championship | NCAA Regional Semifinal |
| 12/11/2021 | H | 8 | Georgia Tech | W | 3 | 1 | 32-0 | 18-0 | 5,917 | Louisville, Ky. | Freedom Hall | NCAA Volleyball Championship | NCAA Regional Final |
| 12/16/2021 | N | 4 | Wisconsin | L | 2 | 3 | 32-1 | 18-0 | Columbus, Ohio | Nationwide Arena | NCAA Volleyball Championship | NCAA National Semifinal |