| 1. Round | 24/07/2021 | CF Pachuca | - | Club León | 4:0 | ||||
| 2. Round | 31/07/2021 | Mazatlán FC | - | CF Pachuca | 2:1 | ||||
| 3. Round | 10/08/2021 | CF Pachuca | - | Atlas Guadalajara | 0:1 |  |
|||
| 4. Round | 15/08/2021 | CF Monterrey | - | CF Pachuca | 3:1 |  |
|||
| 6. Round | 23/08/2021 | Gallos Blancos | - | CF Pachuca | 0:2 | ||||
| 7. Round | 30/08/2021 | Cruz Azul | - | CF Pachuca | 1:1 | |
|||
| 8. Round | 14/09/2021 | CF Pachuca | - | Deportivo Toluca | 1:2 | ||||
| 9. Round | 19/09/2021 | Deportivo Guadalajara | - | CF Pachuca | 1:0 | ||||
| 11. Round | 29/09/2021 | CF Pachuca | - | CF América | 1:1 | ||||
| 13. Round | 17/10/2021 | CF Pachuca | - | Santos Laguna | 1:1 | |
|||
| 14. Round | 21/10/2021 | UANL Tigres | - | CF Pachuca | 3:0 | |
|||
| 15. Round | 25/10/2021 | CF Pachuca | - | FC Juárez | 1:1 | ||||
| 16. Round | 31/10/2021 | CF Pachuca | - | Pumas UNAM | 1:1 | |
|||
| 5. Round | 04/11/2021 | CF Pachuca | - | Atlético San Luis | 0:0 | ||||
| 17. Round | 07/11/2021 | Club Tijuana | - | CF Pachuca | 3:2 | |
Colombia