| 1. Jornada | 26.07.2021 | CF Monterrey | - | Puebla FC | 1:1 |  |
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| 2. Jornada | 31.07.2021 | Puebla FC | - | Deportivo Guadalajara | 0:2 | ||||
| 3. Jornada | 08.08.2021 | CF América | - | Puebla FC | 2:0 | ||||
| 4. Jornada | 14.08.2021 | Puebla FC | - | UANL Tigres | 1:1 | ||||
| 5. Jornada | 18.08.2021 | Club Tijuana | - | Puebla FC | 1:1 | ||||
| 6. Jornada | 22.08.2021 | Pumas UNAM | - | Puebla FC | 2:0 | ||||
| 7. Jornada | 28.08.2021 | Puebla FC | - | Gallos Blancos | 1:0 | ||||
| 8. Jornada | 11.09.2021 | Puebla FC | - | Atlético San Luis | 2:2 | ||||
| 10. Jornada | 25.09.2021 | Puebla FC | - | Cruz Azul | 1:1 | ||||
| 11. Jornada | 29.09.2021 | Atlas Guadalajara | - | Puebla FC | 0:1 | ||||
| 12. Jornada | 02.10.2021 | Puebla FC | - | CF Pachuca | 1:2 | ||||
| 13. Jornada | 16.10.2021 | Club Necaxa | - | Puebla FC | 0:1 | ||||
| 14. Jornada | 20.10.2021 | Puebla FC | - | Mazatlán FC | 2:0 | ||||
| 15. Jornada | 24.10.2021 | Puebla FC | - | Club León | 0:1 | ||||
| 16. Jornada | 30.10.2021 | FC Juárez | - | Puebla FC | 0:2 | ||||
| 17. Jornada | 06.11.2021 | Puebla FC | - | Deportivo Toluca | 1:0 |
Uruguay