| 1. Round | 14/08/2021 | RWD Molenbeek | - | Royal Excel Mouscron | 3:1 |  |
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| 3. Round | 29/08/2021 | Royal Excel Mouscron | - | Waasland-Beveren | 0:4 | ||||
| 4. Round | 10/09/2021 | SK Deinze | - | Royal Excel Mouscron | 3:1 | ||||
| 5. Round | 18/09/2021 | Royal Excel Mouscron | - | Excelsior Virton | 1:1 |  |
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| 6. Round | 26/09/2021 | Royal Excel Mouscron | - | KVC Westerlo | 1:2 | ||||
| 7. Round | 02/10/2021 | Lierse Kempenzonen | - | Royal Excel Mouscron | 2:2 | ||||
| 8. Round | 17/10/2021 | Lommel SK | - | Royal Excel Mouscron | 3:0 | ||||
| 9. Round | 22/10/2021 | Royal Excel Mouscron | - | RWD Molenbeek | 1:1 | |
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| 10. Round | 29/10/2021 | Excelsior Virton | - | Royal Excel Mouscron | 0:2 | ||||
| 11. Round | 06/11/2021 | Royal Excel Mouscron | - | SK Deinze | 2:0 | |
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| 12. Round | 19/11/2021 | Waasland-Beveren | - | Royal Excel Mouscron | 0:2 | ||||
| 13. Round | 28/11/2021 | Royal Excel Mouscron | - | Lierse Kempenzonen | 2:1 | |
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| 14. Round | 05/12/2021 | KVC Westerlo | - | Royal Excel Mouscron | 4:3 | ||||
| 15. Round | 11/12/2021 | Royal Excel Mouscron | - | Lommel SK | 2:1 | ||||
| 16. Round | 18/12/2021 | SK Deinze | - | Royal Excel Mouscron | 2:2 | |
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