| 1. Round | 13/08/2021 | Go Ahead Eagles | - | sc Heerenveen | 0:1 | ||||
| 2. Round | 21/08/2021 | sc Heerenveen | - | RKC Waalwijk | 3:2 | ||||
| 3. Round | 29/08/2021 | sc Heerenveen | - | AZ Alkmaar | 1:3 | ||||
| 4. Round | 12/09/2021 | FC Groningen | - | sc Heerenveen | 1:1 | ||||
| 5. Round | 18/09/2021 | sc Heerenveen | - | Fortuna Sittard | 1:0 | ||||
| 6. Round | 22/09/2021 | Feyenoord | - | sc Heerenveen | 3:1 |  |
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| 7. Round | 26/09/2021 | sc Heerenveen | - | FC Twente | 2:3 |  |
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| 8. Round | 02/10/2021 | PEC Zwolle | - | sc Heerenveen | 0:1 | ||||
| 9. Round | 16/10/2021 | sc Heerenveen | - | AFC Ajax | 0:2 | ||||
| 10. Round | 23/10/2021 | FC Utrecht | - | sc Heerenveen | 2:1 | ||||
| 11. Round | 30/10/2021 | sc Heerenveen | - | Vitesse | 1:2 | ||||
| 12. Round | 06/11/2021 | NEC Nijmegen | - | sc Heerenveen | 1:1 | |
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| 13. Round | 21/11/2021 | sc Heerenveen | - | Willem II | 2:1 | ||||
| 14. Round | 28/11/2021 | sc Heerenveen | - | PSV Eindhoven | 1:1 | ||||
| 15. Round | 04/12/2021 | Heracles Almelo | - | sc Heerenveen | 0:1 | |
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| 16. Round | 11/12/2021 | sc Heerenveen | - | Sparta Rotterdam | 0:0 | ||||
| 17. Round | 19/12/2021 | SC Cambuur | - | sc Heerenveen | 1:2 | ||||
| 18. Round | 22/12/2021 | sc Heerenveen | - | Feyenoord | 0:3 |
Netherlands