| 9/4/2021 | Cal Poly | 28 | at | San Diego (7-4) | 17 | at Pio | ||
| 9/11/2021 | Cal Poly | 10 | at | Fresno State (10-3) | 63 | at MW | ||
| 9/18/2021 | South Dakota (7-5) | 48 | at | Cal Poly | 14 | MVC | ||
| 9/25/2021 | Cal Poly | 7 | at | Montana (10-3,7-2) | 39 | |||
| 10/2/2021 | Weber State (6-5,5-3) | 38 | at | Cal Poly | 7 | |||
| 10/9/2021 | Cal Poly | 7 | at | Montana State (12-3,7-1) | 45 | |||
| 10/23/2021 | UC Davis (8-4,5-3) | 24 | at | Cal Poly | 13 | |||
| 10/30/2021 | Cal Poly | 21 | at | Portland State (5-6,4-4) | 42 | |||
| 11/6/2021 | Cal Poly | 9 | at | Sacramento State (9-3,8-0) | 41 | |||
| 11/13/2021 | Idaho State (1-10,1-7) | 29 | at | Cal Poly | 32 | |||
| 11/20/2021 | Northern Arizona (5-6,4-4) | 45 | at | Cal Poly | 21 |
| vs Cal Poly | vs Other Opponents | Cal Poly compared to OOs | |
| Record: | 9-2 | 71-50 | |
| Points Scored: | 39.18 | 26.57 | -12.61 |
| Points Allowed: | 15.36 | 23.21 | -7.85 |
| Margin: | 23.82 | 3.36 | -20.46 |
| Total Points: | 54.54 | 49.78 | 4.76 |