| 2. Round | 31/07/2021 | Club León | - | Club Tijuana | 2:1 | ||||
| 3. Round | 06/08/2021 | Gallos Blancos | - | Club León | 0:1 | ||||
| 4. Round | 15/08/2021 | Club León | - | Mazatlán FC | 3:0 | ||||
| 5. Round | 19/08/2021 | Deportivo Guadalajara | - | Club León | 0:3 | ||||
| 6. Round | 22/08/2021 | Club León | - | Santos Laguna | 1:1 | ||||
| 7. Round | 29/08/2021 | Club León | - | CF América | 1:1 | ||||
| 8. Round | 12/09/2021 | UANL Tigres | - | Club León | 2:2 | ||||
| 9. Round | 18/09/2021 | Club León | - | FC Juárez | 0:1 | ||||
| 10. Round | 25/09/2021 | Atlas Guadalajara | - | Club León | 2:0 | ||||
| 12. Round | 02/10/2021 | Club León | - | Atlético San Luis | 0:0 | ||||
| 13. Round | 16/10/2021 | CF Monterrey | - | Club León | 0:1 | ||||
| 15. Round | 23/10/2021 | Puebla FC | - | Club León | 0:1 | ||||
| 16. Round | 31/10/2021 | Deportivo Toluca | - | Club León | 0:0 | ||||
| 11. Round | 04/11/2021 | Cruz Azul | - | Club León | 0:1 | ||||
| 17. Round | 06/11/2021 | Club León | - | Club Necaxa | 3:0 |
Colombia