| 1. Round | 25/07/2021 | MŠK Žilina | - | ŠKF Sereď | 3:0 |  |
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| 2. Round | 01/08/2021 | Zlaté Moravce | - | MŠK Žilina | 0:1 | |
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| 3. Round | 08/08/2021 | MŠK Žilina | - | FK Pohronie | 3:1 | |
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| 4. Round | 15/08/2021 | Tatran Liptovský Mikuláš | - | MŠK Žilina | 2:1 | ||||
| 5. Round | 22/08/2021 | MŠK Žilina | - | FK Senica | 3:0 | ||||
| 7. Round | 11/09/2021 | MŠK Žilina | - | AS Trenčín | 1:3 | ||||
| 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 |  |
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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 | ||||
| 17. Round | 05/12/2021 | MŠK Žilina | - | Spartak Trnava | 0:1 | ||||
| 18. Round | 11/12/2021 | AS Trenčín | - | MŠK Žilina | 1:3 |
Slovakia