| 3. Round | 08/08/2021 | MŠK Žilina | - | FK Pohronie | 3:1 | ||||
| 5. Round | 22/08/2021 | MŠK Žilina | - | FK Senica | 3:0 | ||||
| 6. Round | 29/08/2021 | Spartak Trnava | - | MŠK Žilina | 1:1 | ||||
| 7. Round | 11/09/2021 | MŠK Žilina | - | AS Trenčín | 1:3 |  |
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| 8. Round | 19/09/2021 | Slovan Bratislava | - | MŠK Žilina | 2:2 | ||||
| 9. Round | 25/09/2021 | MŠK Žilina | - | MFK Ružomberok | 0:2 | ||||
| 10. Round | 02/10/2021 | MFK Zemplín Michalovce | - | MŠK Žilina | 1:0 | ||||
| 11. Round | 16/10/2021 | MŠK Žilina | - | FC DAC 1904 | 0:2 | ||||
| 12. Round | 22/10/2021 | ŠKF Sereď | - | MŠK Žilina | 1:1 |  |
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| 13. Round | 30/10/2021 | MŠK Žilina | - | Zlaté Moravce | 4:1 | |
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| 14. Round | 06/11/2021 | FK Pohronie | - | MŠK Žilina | 1:2 | ||||
| 15. Round | 20/11/2021 | MŠK Žilina | - | Tatran Liptovský Mikuláš | 2:2 | |
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| 19. Round | 19/12/2021 | MŠK Žilina | - | Slovan Bratislava | 1:1 | ||||
| 20. Round | 14/02/2022 | MFK Ružomberok | - | MŠK Žilina | 5:1 | ||||
| 21. Round | 19/02/2022 | MŠK Žilina | - | MFK Zemplín Michalovce | 2:1 |
Slovakia