| 9/5/2021 | Notre Dame | 41 | at | Florida State (5-7) | 38 | OT | at ACC | |
| 9/11/2021 | Toledo (7-6) | 29 | at | Notre Dame | 32 | MAC | ||
| 9/18/2021 | Purdue (9-4) | 13 | at | Notre Dame | 27 | B10 | ||
| 9/25/2021 | Notre Dame | 41 | vs | Wisconsin (9-4) | 13 | Chicago IL | vs B10 | |
| 10/2/2021 | Cincinnati (13-1) | 24 | at | Notre Dame | 13 | AAC | ||
| 10/9/2021 | Notre Dame | 32 | at | Virginia Tech (6-7) | 29 | at ACC | ||
| 10/23/2021 | Southern California (4-8) | 16 | at | Notre Dame | 31 | P12 | ||
| 10/30/2021 | North Carolina (6-7) | 34 | at | Notre Dame | 44 | ACC | ||
| 11/6/2021 | Navy (4-8) | 6 | at | Notre Dame | 34 | AAC | ||
| 11/13/2021 | Notre Dame | 28 | at | Virginia (6-6) | 3 | at ACC | ||
| 11/20/2021 | Georgia Tech (3-9) | 0 | at | Notre Dame | 55 | ACC | ||
| 11/27/2021 | Notre Dame | 45 | at | Stanford (3-9) | 14 | at P12 | ||
| 1/1/2022 | Oklahoma State (12-2) | 37 | vs | Notre Dame | 35 | Fiesta Bowl - Glendale AZ | B12 |
| vs Notre Dame | vs Other Opponents | Notre Dame compared to OOs | |
| Record: | 2-11 | 85-67 | |
| Points Scored: | 19.69 | 29.39 | 9.70 |
| Points Allowed: | 35.23 | 24.82 | 10.41 |
| Margin: | -15.54 | 4.57 | 20.11 |
| Total Points: | 54.92 | 54.21 | 0.71 |