| 1. Round | 25/07/2021 | MŠK Žilina | - | ŠKF Sereď | 3:0 | ||||
| 2. Round | 01/08/2021 | Zlaté Moravce | - | MŠK Žilina | 0:1 | ||||
| 3. Round | 08/08/2021 | MŠK Žilina | - | FK Pohronie | 3:1 | ||||
| 4. Round | 15/08/2021 | Tatran Liptovský Mikuláš | - | MŠK Žilina | 2:1 | ||||
| 5. Round | 22/08/2021 | MŠK Žilina | - | FK Senica | 3:0 | ||||
| 6. Round | 29/08/2021 | Spartak Trnava | - | MŠK Žilina | 1:1 | ||||
| 8. Round | 19/09/2021 | Slovan Bratislava | - | MŠK Žilina | 2:2 | ||||
| 11. Round | 16/10/2021 | MŠK Žilina | - | FC DAC 1904 | 0:2 | ||||
| 12. Round | 22/10/2021 | ŠKF Sereď | - | MŠK Žilina | 1:1 | ||||
| 13. Round | 30/10/2021 | MŠK Žilina | - | Zlaté Moravce | 4:1 | ||||
| 14. Round | 06/11/2021 | FK Pohronie | - | MŠK Žilina | 1:2 | ||||
| 19. Round | 19/12/2021 | MŠK Žilina | - | Slovan Bratislava | 1:1 |  |
Slovakia