| 2. Round | 21/08/2021 | Sparta Rotterdam | - | Heracles Almelo | 1:1 | ||||
| 3. Round | 29/08/2021 | Heracles Almelo | - | NEC Nijmegen | 0:1 | ||||
| 5. Round | 19/09/2021 | Heracles Almelo | - | AZ Alkmaar | 3:2 | ||||
| 6. Round | 23/09/2021 | SC Cambuur | - | Heracles Almelo | 2:1 | ||||
| 7. Round | 26/09/2021 | Heracles Almelo | - | RKC Waalwijk | 1:0 | ||||
| 8. Round | 02/10/2021 | Heracles Almelo | - | Willem II | 3:2 |  |
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| 10. Round | 23/10/2021 | PEC Zwolle | - | Heracles Almelo | 1:0 | ||||
| 11. Round | 30/10/2021 | Heracles Almelo | - | AFC Ajax | 0:0 | ||||
| 12. Round | 05/11/2021 | FC Twente | - | Heracles Almelo | 1:0 | ||||
| 13. Round | 20/11/2021 | Heracles Almelo | - | Fortuna Sittard | 3:1 | |
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| 14. Round | 28/11/2021 | FC Utrecht | - | Heracles Almelo | 1:0 | ||||
| 4. Round | 01/12/2021 | Feyenoord | - | Heracles Almelo | 2:1 |
Belgium
Morocco