Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-05 | Notre Dame | 41 | Florida State | 38 | Final(OT) | W | 3 |
| 2 | 2021-09-11 | Toledo | 29 | Notre Dame | 32 | Final | W | 3 |
| 3 | 2021-09-18 | Purdue | 13 | Notre Dame | 27 | Final | W | 14 |
| 4 | 2021-09-25 | Notre Dame | 41 | Wisconsin | 13 | Final | W | 28 |
| 5 | 2021-10-02 | Cincinnati | 24 | Notre Dame | 13 | Final | L | -11 |
| 6 | 2021-10-09 | Notre Dame | 32 | Virginia Tech | 29 | Final | W | 3 |
| 7 | 2021-10-23 | USC | 16 | Notre Dame | 31 | Final | W | 15 |
| 8 | 2021-10-30 | North Carolina | 34 | Notre Dame | 44 | Final | W | 10 |
| 9 | 2021-11-06 | Navy | 6 | Notre Dame | 34 | Final | W | 28 |
| 10 | 2021-11-13 | Notre Dame | 28 | Virginia | 3 | Final | W | 25 |
| 11 | 2021-11-20 | Georgia Tech | 0 | Notre Dame | 55 | Final | W | 55 |
| 12 | 2021-11-27 | Notre Dame (5) | 45 | Stanford (107) | 14 | Final | W | 31 |
| 13 | 2022-01-01 | Oklahoma State (6) | 37 | Notre Dame (8) | 35 | Final | L | -2 |