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* All times Eastern
* FBS Rankings reflect the AP Poll
* Notre Dame is playing as a member of the ACC for the 2020-21 season.
| Time | Game | Network |
| Friday, September 18 | ||
| 7:30 | Campbell at Coastal Carolina | ESPN |
| Saturday, September 19 | ||
| Noon | Tulsa at (11) Oklahoma State | ESPN |
| Noon | Austin Peay at (13) Cinconnati | ESPN+ |
| Noon | (19) Louisiana at Georgia State | ESPN2 |
| Noon | Syracuse at (25) Pittsburgh | ACC Network |
| Noon | Houston at Baylor | FOX |
| Noon | Liberty at Western Kentucky | ESPN-U |
| Noon | Navy at Tulane | ABC |
| Noon | Boston College at Duke | ESPN3 |
| 2:30 p.m. | South Florida at (7) Notre Dame | USA |
| 3:00 p.m. | Stephen F. Austin at UTSA | ESPN3 |
| 3:30 p.m. | Charlotte at (12) North Carolina | ESPN3 |
| 3:30 p.m. | (14) UCF at Georgia Tech | ABC |
| 3:30 p.m. | (23) Appalachian State at Marshall | CBS |
| 3:30 p.m. | FAU at Georgia Southern | ESPN |
| 4:00 p.m. | The Citadel at (1) Clemson | ACC Network |
| 4:00 p.m. | Troy at MTSU | ESPN-2 |
| 6:00 p.m. | SMU at North Texas | CBSSN |
| 7:00 p.m. | Central Arkansas at Arkansas State | ESPN+ |
| 7:30 p.m. | (17) Miami at (18) Louisville | ABC |
| 7:30 p.m. | Louisiana Tech at Southern Miss | ESPN2 |
| 7:30 p.m. | Texas State at Louisiana-Monroe | ESPNU |
| 8:00 p.m. | Wake Forest at N.C. State | ACC Network |
| 9:00 p.m. | Abielene Christian at UTEP | ESPN3 |