| 9/4/2021 | Lake Erie | 31 | at | Clarion (0-10) | 26 | at PSAC | ||
| 9/11/2021 | Lake Erie | 31 | at | Franklin Pierce (0-10) | 20 | at NE10 | ||
| 9/18/2021 | Lake Erie | 17 | at | McKendree (4-7) | 10 | at GLV | ||
| 9/25/2021 | Southwest Baptist (4-7) | 28 | at | Lake Erie | 20 | GLV | ||
| 10/2/2021 | Findlay (8-4,6-1) | 37 | at | Lake Erie | 10 | |||
| 10/9/2021 | Tiffin (8-3,5-2) | 35 | at | Lake Erie | 17 | |||
| 10/16/2021 | Lake Erie | 33 | at | Hillsdale (6-6,5-2) | 14 | |||
| 10/23/2021 | Lake Erie | 41 | at | Ashland (5-5,4-3) | 42 | |||
| 10/30/2021 | Kentucky Wesleyan (3-8,1-6) | 28 | at | Lake Erie | 38 | |||
| 11/6/2021 | Lake Erie | 0 | at | Ohio Dominican (7-4,4-3) | 31 | |||
| 11/13/2021 | Walsh (2-9,1-6) | 24 | at | Lake Erie | 7 |
| vs Lake Erie | vs Other Opponents | Lake Erie compared to OOs | |
| Record: | 6-5 | 41-68 | |
| Points Scored: | 26.82 | 24.84 | -1.98 |
| Points Allowed: | 22.27 | 30.70 | -8.43 |
| Margin: | 4.55 | -5.86 | -10.41 |
| Total Points: | 49.09 | 55.54 | -6.45 |