| 2. Round | 31/07/2021 | FK Pohronie | - | MFK Zemplín Michalovce | 2:0 | ||||
| 3. Round | 07/08/2021 | MFK Zemplín Michalovce | - | AS Trenčín | 1:2 | ||||
| 5. Round | 21/08/2021 | MFK Zemplín Michalovce | - | Tatran Liptovský Mikuláš | 2:1 | ||||
| 6. Round | 28/08/2021 | MFK Ružomberok | - | MFK Zemplín Michalovce | 0:0 | ||||
| 7. Round | 11/09/2021 | MFK Zemplín Michalovce | - | Spartak Trnava | 1:2 | ||||
| 8. Round | 18/09/2021 | MFK Zemplín Michalovce | - | Zlaté Moravce | 2:1 | ||||
| 9. Round | 25/09/2021 | ŠKF Sereď | - | MFK Zemplín Michalovce | 0:1 |  |
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| 10. Round | 02/10/2021 | MFK Zemplín Michalovce | - | MŠK Žilina | 1:0 | ||||
| 11. Round | 16/10/2021 | FK Senica | - | MFK Zemplín Michalovce | 1:1 | ||||
| 13. Round | 30/10/2021 | MFK Zemplín Michalovce | - | FK Pohronie | 0:2 | ||||
| 15. Round | 21/11/2021 | MFK Zemplín Michalovce | - | Slovan Bratislava | 1:2 | ||||
| 16. Round | 27/11/2021 | Tatran Liptovský Mikuláš | - | MFK Zemplín Michalovce | 0:1 | ||||
| 17. Round | 04/12/2021 | MFK Zemplín Michalovce | - | MFK Ružomberok | 0:3 | ||||
| 18. Round | 10/12/2021 | Spartak Trnava | - | MFK Zemplín Michalovce | 2:0 | ||||
| 19. Round | 18/12/2021 | Zlaté Moravce | - | MFK Zemplín Michalovce | 0:1 |
Slovakia