Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | San Jose State | 7 | USC | 30 | Final | W | 23 |
| 2 | 2021-09-11 | Stanford | 42 | USC | 28 | Final | L | -14 |
| 3 | 2021-09-18 | USC | 45 | Washington State | 14 | Final | W | 31 |
| 4 | 2021-09-25 | Oregon State | 45 | USC | 27 | Final | L | -18 |
| 5 | 2021-10-02 | USC | 37 | Colorado | 14 | Final | W | 23 |
| 6 | 2021-10-09 | Utah | 42 | USC | 26 | Final | L | -16 |
| 7 | 2021-10-23 | USC | 16 | Notre Dame | 31 | Final | L | -15 |
| 8 | 2021-10-30 | Arizona | 34 | USC | 41 | Final | W | 7 |
| 9 | 2021-11-06 | USC | 16 | Arizona State | 31 | Final | L | -15 |
| 10 | 2021-11-20 | UCLA | 62 | USC | 33 | Final | L | -29 |
| 11 | 2021-11-27 | BYU (18) | 35 | USC (86) | 31 | Final | L | -4 |
| 12 | 2021-12-04 | USC (90) | 14 | California (93) | 24 | Final | L | -10 |