| 1. Round | 25/07/2021 | Spartak Trnava | - | FK Pohronie | 2:0 | ||||
| 2. Round | 01/08/2021 | FK Senica | - | Spartak Trnava | 2:1 | ||||
| 3. Round | 09/08/2021 | Spartak Trnava | - | Tatran Liptovský Mikuláš | 4:0 | ||||
| 4. Round | 15/08/2021 | Spartak Trnava | - | Zlaté Moravce | 2:0 | ||||
| 5. Round | 21/08/2021 | MFK Ružomberok | - | Spartak Trnava | 0:0 | ||||
| 6. Round | 29/08/2021 | Spartak Trnava | - | MŠK Žilina | 1:1 |  |
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| 7. Round | 11/09/2021 | MFK Zemplín Michalovce | - | Spartak Trnava | 1:2 | |
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| 8. Round | 17/09/2021 | Spartak Trnava | - | ŠKF Sereď | 2:0 | |
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| 9. Round | 26/09/2021 | FC DAC 1904 | - | Spartak Trnava | 0:3 | ||||
| 10. Round | 03/10/2021 | AS Trenčín | - | Spartak Trnava | 0:1 | |
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| 11. Round | 17/10/2021 | Spartak Trnava | - | Slovan Bratislava | 0:3 dec. | ||||
| 17. Round | 05/12/2021 | MŠK Žilina | - | Spartak Trnava | 0:1 | ||||
| 18. Round | 10/12/2021 | Spartak Trnava | - | MFK Zemplín Michalovce | 2:0 | ||||
| 19. Round | 18/12/2021 | ŠKF Sereď | - | Spartak Trnava | 0:1 |
Czech Republic