| 1. Round | 25/07/2021 | Deportivo Guadalajara | - | Atlético San Luis | 1:2 | ||||
| 2. Round | 31/07/2021 | Puebla FC | - | Deportivo Guadalajara | 0:2 | ||||
| 3. Round | 07/08/2021 | Deportivo Guadalajara | - | FC Juárez | 2:2 | ||||
| 4. Round | 16/08/2021 | Santos Laguna | - | Deportivo Guadalajara | 0:0 | ||||
| 5. Round | 19/08/2021 | Deportivo Guadalajara | - | Club León | 0:3 | ||||
| 8. Round | 12/09/2021 | Pumas UNAM | - | Deportivo Guadalajara | 0:0 | ||||
| 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 | ||||
| 13. Round | 17/10/2021 | Deportivo Guadalajara | - | Deportivo Toluca | 2:0 | ||||
| 14. Round | 21/10/2021 | Club Tijuana | - | Deportivo Guadalajara | 0:0 | ||||
| 15. Round | 24/10/2021 | Deportivo Guadalajara | - | Cruz Azul | 1:1 | ||||
| 16. Round | 31/10/2021 | UANL Tigres | - | Deportivo Guadalajara | 2:1 |
Mexico