Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Missouri State | 16 | Oklahoma State | 23 | Final | W | 7 |
| 2 | 2021-09-11 | Tulsa | 23 | Oklahoma State | 28 | Final | W | 5 |
| 3 | 2021-09-18 | Oklahoma State | 21 | Boise State | 20 | Final | W | 1 |
| 4 | 2021-09-25 | Kansas State | 20 | Oklahoma State | 31 | Final | W | 11 |
| 5 | 2021-10-02 | Baylor | 14 | Oklahoma State | 17 | Final | W | 3 |
| 6 | 2021-10-16 | Oklahoma State | 32 | Texas | 24 | Final | W | 8 |
| 7 | 2021-10-23 | Oklahoma State | 21 | Iowa State | 24 | Final | L | -3 |
| 8 | 2021-10-30 | Kansas | 3 | Oklahoma State | 55 | Final | W | 52 |
| 9 | 2021-11-06 | Oklahoma State | 24 | West Virginia | 3 | Final | W | 21 |
| 10 | 2021-11-13 | TCU | 16 | Oklahoma State | 63 | Final | W | 47 |
| 11 | 2021-11-13 | TCU | 17 | Oklahoma State | 63 | Final | W | 46 |
| 12 | 2021-11-20 | Oklahoma State | 23 | Texas Tech | 0 | Final | W | 23 |
| 13 | 2021-11-27 | Oklahoma (10) | 33 | Oklahoma State (7) | 37 | Final | W | 4 |
| 14 | 2021-12-04 | Oklahoma State | 0 | Baylor | 0 | Cancelled | - | - |
| 15 | 2021-12-04 | Baylor (8) | 21 | Oklahoma State (7) | 16 | Final | L | -5 |
| 16 | 2022-01-01 | Oklahoma State (6) | 37 | Notre Dame (8) | 35 | Final | W | 2 |