| 9/3/2021 | Old Dominion | 10 | at | Wake Forest (11-3) | 42 | at ACC | ||
| 9/11/2021 | Hampton (5-6) | 7 | at | Old Dominion | 47 | BigS (1AA) | ||
| 9/18/2021 | Old Dominion | 17 | at | Liberty (8-5) | 45 | at Ind | ||
| 9/25/2021 | Buffalo (4-8) | 35 | at | Old Dominion | 34 | MAC | ||
| 10/2/2021 | Old Dominion | 21 | at | UTEP (7-6,4-4) | 28 | |||
| 10/9/2021 | Old Dominion | 13 | at | Marshall (7-6,5-3) | 20 | OT | ||
| 10/16/2021 | Western Kentucky (9-5,7-2) | 43 | at | Old Dominion | 20 | |||
| 10/30/2021 | Louisiana Tech (3-9,2-6) | 20 | at | Old Dominion | 23 | |||
| 11/6/2021 | Old Dominion | 47 | at | Florida Intl (1-11,0-8) | 24 | |||
| 11/13/2021 | Florida Atlantic (5-7,3-5) | 16 | at | Old Dominion | 30 | |||
| 11/20/2021 | Old Dominion | 24 | at | Middle Tenn State (7-6,4-4) | 17 | |||
| 11/27/2021 | UNC-Charlotte (5-7,3-5) | 34 | at | Old Dominion | 56 | |||
| 12/20/2021 | Old Dominion | 17 | vs | Tulsa (7-6) | 30 | Myrtle Beach Bowl - Conway SC | vs AAC |
| vs Old Dominion | vs Other Opponents | Old Dominion compared to OOs | |
| Record: | 7-6 | 72-79 | |
| Points Scored: | 27.77 | 30.63 | 2.86 |
| Points Allowed: | 27.62 | 28.87 | -1.25 |
| Margin: | 0.15 | 1.76 | 1.61 |
| Total Points: | 55.39 | 59.50 | -4.11 |