| 9/5/2021 | Notre Dame | 41 | at | Florida State | 38 | OT | @ ACC | |
| 9/11/2021 | Toledo | 29 | at | Notre Dame | 32 | MAC | ||
| 9/18/2021 | Purdue | 13 | at | Notre Dame | 27 | B10 | ||
| 9/25/2021 | Notre Dame | 41 | vs | Wisconsin | 13 | Chicago IL | vs B10 | |
| 10/2/2021 | Cincinnati | 24 | at | Notre Dame | 13 | AAC | ||
| 10/9/2021 | Notre Dame | 32 | at | Virginia Tech | 29 | @ ACC | ||
| 10/23/2021 | Southern California | 16 | at | Notre Dame | 31 | P12 | ||
| 10/30/2021 | North Carolina | 34 | at | Notre Dame | 44 | ACC | ||
| 11/6/2021 | Navy | 6 | at | Notre Dame | 34 | AAC | ||
| 11/13/2021 | Notre Dame | 28 | at | Virginia | 3 | @ ACC | ||
| 11/20/2021 | Georgia Tech | 0 | at | Notre Dame | 55 | ACC | ||
| 11/27/2021 | Notre Dame | 45 | at | Stanford | 14 | @ P12 | ||
| 1/1/2022 | Oklahoma State | 37 | vs | Notre Dame | 35 | Fiesta Bowl - Glendale AZ | vs B12 |