| 1. Round | 27/07/2021 | Cruz Azul | - | Mazatlán FC | 0:2 |  |
|||
| 2. Round | 31/07/2021 | Mazatlán FC | - | CF Pachuca | 2:1 |  |
|||
| 3. Round | 07/08/2021 | Mazatlán FC | - | CF Monterrey | 1:1 | ||||
| 4. Round | 15/08/2021 | Club León | - | Mazatlán FC | 3:0 | |
|||
| 5. Round | 17/08/2021 | Deportivo Toluca | - | Mazatlán FC | 2:2 | |
|||
| 6. Round | 21/08/2021 | Mazatlán FC | - | UANL Tigres | 0:3 | ||||
| 7. Round | 28/08/2021 | Mazatlán FC | - | Atlético San Luis | 2:2 | ||||
| 8. Round | 12/09/2021 | CF América | - | Mazatlán FC | 2:0 | |
|||
| 9. Round | 19/09/2021 | Mazatlán FC | - | Pumas UNAM | 2:2 | ||||
| 10. Round | 25/09/2021 | Club Tijuana | - | Mazatlán FC | 0:0 | ||||
| 11. Round | 29/09/2021 | Mazatlán FC | - | FC Juárez | 3:1 | ||||
| 12. Round | 03/10/2021 | Santos Laguna | - | Mazatlán FC | 1:0 | |
|||
| 14. Round | 20/10/2021 | Puebla FC | - | Mazatlán FC | 2:0 | ||||
| 15. Round | 23/10/2021 | Mazatlán FC | - | Gallos Blancos | 2:1 | ||||
| 16. Round | 30/10/2021 | Club Necaxa | - | Mazatlán FC | 2:1 | ||||
| 17. Round | 06/11/2021 | Mazatlán FC | - | Deportivo Guadalajara | 0:1 | |
Chile