| Date | Week | Home | Score | Away | Score | |
| 8/20/2021 | 1 | Riverdale (NC) | 14 | Southwestern/East Dubuque, IL | 22 | |
| 8/27/2021 | 2 | Boscobel (NC) | 12 | Southwestern/East Dubuque, IL | 22 | |
| 9/3/2021 | 3 | Southwestern/East Dubuque, IL | 7 | Potosi/Cassville | 50 | |
| 9/10/2021 | 4 | Southwestern/East Dubuque, IL | 28 | Iowa-Grant | 12 | |
| 9/17/2021 | 5 | River Ridge | 41 | Southwestern/East Dubuque, IL | 3 | |
| 9/24/2021 | 6 | Southwestern/East Dubuque, IL | 0 | Black Hawk/Warren, IL | 54 | |
| 10/1/2021 | 7 | Lancaster | 1 | Southwestern/East Dubuque, IL | 0 | |
| 10/9/2021 | 8 | Pecatonica/Argyle | 1 | Southwestern/East Dubuque, IL | 0 | |
| 10/15/2021 | 9 | Benton/Scales Mound IL/Shullsburg | 1 | Southwestern/East Dubuque, IL | 0 | |