| 1. Round | 25/07/2021 | Deportivo Guadalajara | - | Atlético San Luis | 1:2 | ||||
| 2. Round | 31/07/2021 | Puebla FC | - | Deportivo Guadalajara | 0:2 |  |
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| 3. Round | 07/08/2021 | Deportivo Guadalajara | - | FC Juárez | 2:2 | ||||
| 4. Round | 16/08/2021 | Santos Laguna | - | Deportivo Guadalajara | 0:0 | |
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| 6. Round | 22/08/2021 | CF Monterrey | - | Deportivo Guadalajara | 0:0 | ||||
| 7. Round | 28/08/2021 | Deportivo Guadalajara | - | Club Necaxa | 2:1 | ||||
| 8. Round | 12/09/2021 | Pumas UNAM | - | Deportivo Guadalajara | 0:0 | ||||
| 9. Round | 19/09/2021 | Deportivo Guadalajara | - | CF Pachuca | 1:0 | ||||
| 10. Round | 26/09/2021 | CF América | - | Deportivo Guadalajara | 0:0 | ||||
| 11. Round | 30/09/2021 | Gallos Blancos | - | Deportivo Guadalajara | 1:0 | ||||
| 12. Round | 03/10/2021 | Deportivo Guadalajara | - | Atlas Guadalajara | 0:1 |
Mexico