| 5. Round | 18/08/2021 | Club Necaxa | - | Pumas UNAM | 3:0 | ||||
| 6. Round | 22/08/2021 | Pumas UNAM | - | Puebla FC | 2:0 | ||||
| 7. Round | 29/08/2021 | Deportivo Toluca | - | Pumas UNAM | 2:1 | ||||
| 8. Round | 12/09/2021 | Pumas UNAM | - | Deportivo Guadalajara | 0:0 | ||||
| 9. Round | 19/09/2021 | Mazatlán FC | - | Pumas UNAM | 2:2 | ||||
| 10. Round | 26/09/2021 | UANL Tigres | - | Pumas UNAM | 0:0 | ||||
| 12. Round | 03/10/2021 | CF América | - | Pumas UNAM | 2:0 |  |
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| 13. Round | 17/10/2021 | Pumas UNAM | - | FC Juárez | 1:0 | ||||
| 14. Round | 21/10/2021 | Club León | - | Pumas UNAM | 1:2 | ||||
| 15. Round | 24/10/2021 | Pumas UNAM | - | Club Tijuana | 3:1 |  |
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| 16. Round | 31/10/2021 | CF Pachuca | - | Pumas UNAM | 1:1 | ||||
| 11. Round | 05/11/2021 | Pumas UNAM | - | Santos Laguna | 0:3 | |
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| 17. Round | 07/11/2021 | Pumas UNAM | - | Cruz Azul | 4:3 | |
Mexico