| 15. Round | 04/12/2021 | Heracles Almelo | - | sc Heerenveen | 0:1 | ||||
| 16. Round | 12/12/2021 | Vitesse | - | Heracles Almelo | 2:1 | ||||
| 17. Round | 18/12/2021 | Heracles Almelo | - | FC Groningen | 4:2 | ||||
| 18. Round | 22/12/2021 | Heracles Almelo | - | SC Cambuur | 1:1 | ||||
| 21. Round | 06/02/2022 | AFC Ajax | - | Heracles Almelo | 3:0 | ||||
| 22. Round | 11/02/2022 | Heracles Almelo | - | FC Utrecht | 1:0 | ||||
| 23. Round | 19/02/2022 | AZ Alkmaar | - | Heracles Almelo | 2:1 | ||||
| 28. Round | 03/04/2022 | Fortuna Sittard | - | Heracles Almelo | 0:2 | ||||
| 29. Round | 10/04/2022 | Heracles Almelo | - | Feyenoord | 1:4 | ||||
| 34. Round | 15/05/2022 | Heracles Almelo | - | Sparta Rotterdam | 1:3 |
Serbia