| 9/2/2021 | East Carolina | 19 | vs | Appalachian State | 33 | Charlotte NC | vs SBC | |
| Boise State | 31 | at | UCF | 36 | MW | |||
| South Florida | 0 | at | North Carolina State | 45 | @ ACC | |||
| UC Davis | 19 | at | Tulsa | 17 | BSky (1AA) | |||
| 9/4/2021 | Miami-Ohio | 14 | at | Cincinnati | 49 | MAC | ||
| Texas Tech | 38 | at | Houston | 21 | B12 | |||
| Nicholls State | 17 | at | Memphis | 42 | SLC (1AA) | |||
| Marshall | 49 | at | Navy | 7 | CUSA | |||
| Tulane | 35 | at | Oklahoma | 40 | @ B12 | |||
| Temple | 14 | at | Rutgers | 61 | @ B10 | |||
| Abilene Christian | 9 | at | SMU | 56 | WAC (1AA) | |||
| 9/11/2021 | Temple | 45 | at | Akron | 24 | @ MAC | ||
| Memphis | 55 | at | Arkansas State | 50 | @ SBC | |||
| Bethune-Cookman | 14 | at | UCF | 63 | SWAC (1AA) | |||
| Murray State | 7 | at | Cincinnati | 42 | OVC (1AA) | |||
| South Carolina | 20 | at | East Carolina | 17 | SEC | |||
| Air Force | 23 | at | Navy | 3 | MW | |||
| Tulsa | 23 | at | Oklahoma State | 28 | @ B12 | |||
| Houston | 44 | at | Rice | 7 | @ CUSA | |||
| North Texas | 12 | at | SMU | 35 | CUSA | |||
| Florida | 42 | at | South Florida | 20 | SEC | |||
| Morgan State | 20 | at | Tulane | 69 | MEAC (1AA) | |||
| 9/17/2021 | UCF | 35 | at | Louisville | 42 | @ ACC | ||
| 9/18/2021 | Grambling | 0 | at | Houston | 45 | SWAC (1AA) | ||
| Cincinnati | 38 | at | Indiana | 24 | @ B10 | |||
| SMU | 39 | at | Louisiana Tech | 37 | @ CUSA | |||
| East Carolina | 42 | at | Marshall | 38 | @ CUSA | |||
| Mississippi State | 29 | at | Memphis | 31 | SEC | |||
| Tulane | 21 | at | Mississippi | 61 | @ SEC | |||
| Tulsa | 20 | at | Ohio State | 41 | @ B10 | |||
| Florida A&M | 17 | at | South Florida | 38 | SWAC (1AA) | |||
| Boston College | 28 | at | Temple | 3 | ACC | |||
| 9/25/2021 | South Florida | 27 | at | BYU | 35 | @ Ind | ||
| Charleston Southern | 28 | at | East Carolina | 31 | BigS (1AA) | |||
| Navy | 20 | at | Houston | 28 | ||||
| Texas-San Antonio | 31 | at | Memphis | 28 | CUSA | |||
| SMU | 42 | at | TCU | 34 | @ B12 | |||
| Wagner | 7 | at | Temple | 41 | NE (1AA) | |||
| UAB | 28 | at | Tulane | 21 | CUSA | |||
| Arkansas State | 34 | at | Tulsa | 41 | SBC | |||
| 10/1/2021 | Houston | 45 | at | Tulsa | 10 | |||
| 10/2/2021 | Tulane | 29 | at | East Carolina | 52 | |||
| UCF | 30 | at | Navy | 34 | ||||
| Cincinnati | 24 | at | Notre Dame | 13 | @ ND | |||
| South Florida | 17 | at | SMU | 41 | ||||
| Memphis | 31 | at | Temple | 34 | ||||
| 10/7/2021 | Houston | 40 | at | Tulane | 22 | |||
| 10/8/2021 | Temple | 3 | at | Cincinnati | 52 | |||
| 10/9/2021 | East Carolina | 16 | at | UCF | 20 | |||
| SMU | 31 | at | Navy | 24 | ||||
| Memphis | 29 | at | Tulsa | 35 | ||||
| 10/14/2021 | Navy | 17 | at | Memphis | 35 | |||
| 10/16/2021 | UCF | 21 | at | Cincinnati | 56 | |||
| Tulsa | 32 | at | South Florida | 31 | ||||
| 10/21/2021 | Tulane | 26 | at | SMU | 55 | |||
| 10/22/2021 | Memphis | 7 | at | UCF | 24 | |||
| 10/23/2021 | East Carolina | 24 | at | Houston | 31 | OT | ||
| Cincinnati | 27 | at | Navy | 20 | ||||
| Temple | 14 | at | South Florida | 34 | ||||
| 10/28/2021 | South Florida | 14 | at | East Carolina | 29 | |||
| 10/29/2021 | Navy | 20 | at | Tulsa | 17 | |||
| 10/30/2021 | SMU | 37 | at | Houston | 44 | |||
| UCF | 49 | at | Temple | 7 | ||||
| Cincinnati | 31 | at | Tulane | 12 | ||||
| 11/6/2021 | Tulane | 10 | at | UCF | 14 | |||
| Tulsa | 20 | at | Cincinnati | 28 | ||||
| Temple | 3 | at | East Carolina | 45 | ||||
| SMU | 25 | at | Memphis | 28 | ||||
| Navy | 6 | at | Notre Dame | 34 | @ ND | |||
| Houston | 54 | at | South Florida | 42 | ||||
| 11/12/2021 | Cincinnati | 45 | at | South Florida | 28 | |||
| 11/13/2021 | East Carolina | 30 | at | Memphis | 29 | OT | ||
| UCF | 28 | at | SMU | 55 | ||||
| Houston | 37 | at | Temple | 8 | ||||
| Tulsa | 20 | at | Tulane | 13 | OT | |||
| 11/19/2021 | Memphis | 13 | at | Houston | 31 | |||
| 11/20/2021 | Connecticut | 17 | at | UCF | 49 | Ind | ||
| SMU | 14 | at | Cincinnati | 48 | ||||
| East Carolina | 38 | at | Navy | 35 | ||||
| South Florida | 14 | at | Tulane | 45 | ||||
| Temple | 10 | at | Tulsa | 44 | ||||
| 11/26/2021 | South Florida | 13 | at | UCF | 17 | |||
| Cincinnati | 35 | at | East Carolina | 13 | ||||
| 11/27/2021 | Houston | 45 | at | Connecticut | 17 | @ Ind | ||
| Tulane | 28 | at | Memphis | 33 | ||||
| Tulsa | 34 | at | SMU | 31 | ||||
| Navy | 38 | at | Temple | 14 | ||||
| 12/4/2021 | Houston | 20 | at | Cincinnati | 35 | AAC Championship | ||
| 12/11/2021 | Army | 13 | vs | Navy | 17 | East Rutherford NJ | vs Ind | |
| 12/20/2021 | Old Dominion | 17 | vs | Tulsa | 30 | Myrtle Beach Bowl - Conway SC | vs CUSA | |
| 12/23/2021 | UCF | 29 | vs | Florida | 17 | Gasparilla Bowl - Saint Petersburg FL | vs SEC | |
| 12/24/2021 | Memphis | vs | Hawaii | Cancelled Hawaii Bowl - Honoluli HI | vs MW | |||
| 12/27/2021 | Boston College | vs | East Carolina | Cancelled Military Bowl - Annapolis MD | vs ACC | |||
| 12/28/2021 | Houston | 17 | vs | Auburn | 13 | Birmingham Bowl - Birmingham AL | vs SEC | |
| 12/29/2021 | SMU | vs | Virginia | Cancelled Wasabi Fenway Bowl - Boston MA | vs ACC | |||
| 12/31/2021 | Cincinnati | 6 | vs | Alabama | 27 | FBS Semifinal - Arlngton TX | vs SEC |