| 1. Round | 25/07/2021 | Slovan Liberec | - | 1. FC Slovácko | 0:1 | ||||
| 6. Round | 28/08/2021 | 1. FC Slovácko | - | FK Pardubice | 2:1 | ||||
| 7. Round | 12/09/2021 | Slavia Praha | - | 1. FC Slovácko | 2:1 | ||||
| 8. Round | 18/09/2021 | 1. FC Slovácko | - | FC Fastav Zlín | 3:0 | ||||
| 9. Round | 26/09/2021 | FK Mladá Boleslav | - | 1. FC Slovácko | 3:5 | ||||
| 10. Round | 02/10/2021 | 1. FC Slovácko | - | FK Teplice | 3:2 |  |
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| 11. Round | 16/10/2021 | Baník Ostrava | - | 1. FC Slovácko | 1:2 | ||||
| 12. Round | 23/10/2021 | 1. FC Slovácko | - | Bohemians Praha 1905 | 1:0 | ||||
| 13. Round | 30/10/2021 | Sigma Olomouc | - | 1. FC Slovácko | 0:3 | ||||
| 14. Round | 07/11/2021 | MFK Karviná | - | 1. FC Slovácko | 2:2 | ||||
| 15. Round | 21/11/2021 | 1. FC Slovácko | - | AC Sparta Praha | 4:0 | ||||
| 16. Round | 27/11/2021 | Dynamo České Budějovice | - | 1. FC Slovácko | 3:2 | ||||
| 17. Round | 05/12/2021 | 1. FC Slovácko | - | Viktoria Plzeň | 1:2 | ||||
| 18. Round | 11/12/2021 | FC Hradec Králové | - | 1. FC Slovácko | 2:2 | ||||
| 19. Round | 18/12/2021 | 1. FC Slovácko | - | FK Jablonec | 2:1 | |
Czech Republic