| 2. Round | 17/01/2021 | Cruz Azul | - | Puebla FC | 0:1 | ||||
| 4. Round | 03/02/2021 | Puebla FC | - | CF Monterrey | 0:0 | ||||
| 5. Round | 07/02/2021 | CF América | - | Puebla FC | 1:0 | ||||
| 6. Round | 13/02/2021 | Puebla FC | - | FC Juárez | 4:0 | ||||
| 7. Round | 21/02/2021 | Gallos Blancos | - | Puebla FC | 1:1 | ||||
| 8. Round | 27/02/2021 | Puebla FC | - | Club Necaxa | 1:0 | ||||
| 9. Round | 03/03/2021 | Club León | - | Puebla FC | 1:2 | ||||
| 11. Round | 13/03/2021 | Puebla FC | - | Atlas Guadalajara | 0:1 | ||||
| 12. Round | 21/03/2021 | Deportivo Toluca | - | Puebla FC | 4:4 |  |
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| 14. Round | 13/04/2021 | CF Pachuca | - | Puebla FC | 1:3 |  |
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| 15. Round | 17/04/2021 | Atlético San Luis | - | Puebla FC | 1:4 | ||||
| 17. Round | 03/05/2021 | Santos Laguna | - | Puebla FC | 0:0 |
Mexico