| 9/4/2021 | Tulane (2-10) | 35 | at | Oklahoma | 40 | AAC | ||
| 9/11/2021 | Western Carolina (4-7) | 0 | at | Oklahoma | 76 | SoCon (1AA) | ||
| 9/18/2021 | Nebraska (3-9) | 16 | at | Oklahoma | 23 | B10 | ||
| 9/25/2021 | West Virginia (6-7,4-5) | 13 | at | Oklahoma | 16 | |||
| 10/2/2021 | Oklahoma | 37 | at | Kansas State (8-5,4-5) | 31 | |||
| 10/9/2021 | Oklahoma | 55 | vs | Texas (5-7,3-6) | 48 | Dallas TX | ||
| 10/16/2021 | TCU (5-7,3-6) | 31 | at | Oklahoma | 52 | |||
| 10/23/2021 | Oklahoma | 35 | at | Kansas (2-10,1-8) | 23 | |||
| 10/30/2021 | Texas Tech (7-6,3-6) | 21 | at | Oklahoma | 52 | |||
| 11/13/2021 | Oklahoma | 14 | at | Baylor (12-2,8-2) | 27 | |||
| 11/20/2021 | Iowa State (7-6,5-4) | 21 | at | Oklahoma | 28 | |||
| 11/27/2021 | Oklahoma | 33 | at | Oklahoma State (12-2,8-2) | 37 | |||
| 12/29/2021 | Oregon (10-4) | 32 | vs | Oklahoma | 47 | Alamo Bowl - San Antonio TX | P12 |
| vs Oklahoma | vs Other Opponents | Oklahoma compared to OOs | |
| Record: | 2-11 | 81-71 | |
| Points Scored: | 25.77 | 29.66 | 3.89 |
| Points Allowed: | 39.08 | 26.66 | 12.42 |
| Margin: | -13.31 | 3.00 | 16.31 |
| Total Points: | 64.85 | 56.32 | 8.53 |