| 3. Round | 28/08/2021 | SC Cambuur | - | FC Twente | 2:0 | ||||
| 4. Round | 11/09/2021 | FC Twente | - | FC Utrecht | 1:0 | ||||
| 5. Round | 19/09/2021 | Vitesse | - | FC Twente | 1:4 |  |
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| 6. Round | 23/09/2021 | FC Twente | - | AZ Alkmaar | 3:1 | ||||
| 7. Round | 26/09/2021 | sc Heerenveen | - | FC Twente | 2:3 | ||||
| 8. Round | 01/10/2021 | FC Groningen | - | FC Twente | 1:1 | ||||
| 12. Round | 05/11/2021 | FC Twente | - | Heracles Almelo | 1:0 | ||||
| 13. Round | 20/11/2021 | Sparta Rotterdam | - | FC Twente | 0:1 | ||||
| 14. Round | 28/11/2021 | FC Twente | - | Feyenoord | 0:0 |
Netherlands