| 1. Round | 24/07/2021 | MFK Ružomberok | - | FK Senica | 0:0 |  |
|||
| 2. Round | 01/08/2021 | FK Senica | - | Spartak Trnava | 2:1 | ||||
| 3. Round | 06/08/2021 | Zlaté Moravce | - | FK Senica | 1:1 |  |
|||
| 5. Round | 22/08/2021 | MŠK Žilina | - | FK Senica | 3:0 | ||||
| 6. Round | 28/08/2021 | Tatran Liptovský Mikuláš | - | FK Senica | 1:2 | ||||
| 7. Round | 11/09/2021 | FK Senica | - | FK Pohronie | 1:0 | ||||
| 8. Round | 18/09/2021 | AS Trenčín | - | FK Senica | 3:3 | ||||
| 10. Round | 02/10/2021 | ŠKF Sereď | - | FK Senica | 2:1 | ||||
| 11. Round | 16/10/2021 | FK Senica | - | MFK Zemplín Michalovce | 1:1 | ||||
| 13. Round | 29/10/2021 | Spartak Trnava | - | FK Senica | 2:1 |
Czech Republic