| 9/3/2021 | Duke | 28 | at | UNC-Charlotte (5-7) | 31 | at CUSA | ||
| 9/10/2021 | North Carolina A&T (5-6) | 17 | at | Duke | 45 | BigS (1AA) | ||
| 9/18/2021 | Northwestern (3-9) | 23 | at | Duke | 30 | B10 | ||
| 9/25/2021 | Kansas (2-10) | 33 | at | Duke | 52 | B12 | ||
| 10/2/2021 | Duke | 7 | at | North Carolina (6-7,4-5) | 38 | |||
| 10/9/2021 | Georgia Tech (3-9,2-6) | 31 | at | Duke | 27 | |||
| 10/16/2021 | Duke | 0 | at | Virginia (6-6,4-4) | 48 | |||
| 10/30/2021 | Duke | 7 | at | Wake Forest (11-3,7-3) | 45 | |||
| 11/6/2021 | Pittsburgh (11-3,8-1) | 54 | at | Duke | 29 | |||
| 11/13/2021 | Duke | 17 | at | Virginia Tech (6-7,4-4) | 48 | |||
| 11/18/2021 | Louisville (6-7,4-4) | 62 | at | Duke | 22 | |||
| 11/27/2021 | Miami-Florida (7-5,5-3) | 47 | at | Duke | 10 |
| vs Duke | vs Other Opponents | Duke compared to OOs | |
| Record: | 9-3 | 62-76 | |
| Points Scored: | 39.75 | 28.92 | -10.83 |
| Points Allowed: | 22.83 | 30.68 | -7.85 |
| Margin: | 16.92 | -1.76 | -18.68 |
| Total Points: | 62.58 | 59.60 | 2.98 |