| 2. Round | 26/08/1980 | FC Twente | - | FC Utrecht | 3:0 | ||||
| 4. Round | 02/09/1980 | Roda JC Kerkrade | - | FC Twente | 6:1 | ||||
| 6. Round | 19/09/1980 | NAC Breda | - | FC Twente | 1:2 | ||||
| 7. Round | 26/09/1980 | FC Twente | - | PSV Eindhoven | 0:1 | ||||
| 8. Round | 05/10/1980 | SBV Excelsior | - | FC Twente | 1:1 | ||||
| 9. Round | 18/10/1980 | FC Twente | - | FC Groningen | 3:1 | ||||
| 10. Round | 25/10/1980 | FC Den Haag | - | FC Twente | 1:0 | ||||
| 11. Round | 31/10/1980 | FC Twente | - | AZ '67 Alkmaar | 1:1 | ||||
| 13. Round | 21/11/1980 | FC Twente | - | SC NEC | 6:1 | ||||
| 14. Round | 29/11/1980 | AFC Ajax | - | FC Twente | 5:3 |  |
|||
| 16. Round | 13/12/1980 | Sparta Rotterdam | - | FC Twente | 1:2 | ||||
| 15. Round | 16/12/1980 | FC Twente | - | MVV | 3:3 | ||||
| 17. Round | 20/12/1980 | Feyenoord | - | FC Twente | 1:0 | ||||
| 21. Round | 18/03/1981 | FC Twente | - | Roda JC Kerkrade | 3:2 | ||||
| 24. Round | 27/03/1981 | PSV Eindhoven | - | FC Twente | 1:0 | ||||
| 26. Round | 11/04/1981 | FC Groningen | - | FC Twente | 0:1 | ||||
| 27. Round | 17/04/1981 | FC Twente | - | FC Den Haag | 4:1 | ||||
| 28. Round | 24/04/1981 | AZ '67 Alkmaar | - | FC Twente | 0:0 | ||||
| 29. Round | 02/05/1981 | FC Twente | - | PEC Zwolle | 2:0 | ||||
| 34. Round | 05/06/1981 | FC Twente | - | Feyenoord | 3:7 |
Netherlands