| 3. Round | 29/01/2022 | Puebla FC | - | Club Tijuana | 3:1 | ||||
| 4. Round | 06/02/2022 | Gallos Blancos | - | Puebla FC | 0:2 | ||||
| 5. Round | 12/02/2022 | Puebla FC | - | Atlas Guadalajara | 1:1 | ||||
| 6. Round | 19/02/2022 | Puebla FC | - | CF Monterrey | 1:0 | ||||
| 7. Round | 27/02/2022 | Deportivo Guadalajara | - | Puebla FC | 2:3 | ||||
| 8. Round | 02/03/2022 | Puebla FC | - | FC Juárez | 1:1 | ||||
| 9. Round | 06/03/2022 | Cruz Azul | - | Puebla FC | 1:3 | ||||
| 10. Round | 13/03/2022 | Atlético San Luis | - | Puebla FC | 2:1 | ||||
| 11. Round | 19/03/2022 | Puebla FC | - | Santos Laguna | 2:2 | ||||
| 12. Round | 03/04/2022 | Deportivo Toluca | - | Puebla FC | 2:1 | ||||
| 13. Round | 09/04/2022 | Puebla FC | - | Pumas UNAM | 2:2 | ||||
| 14. Round | 16/04/2022 | Club León | - | Puebla FC | 0:1 | ||||
| 15. Round | 20/04/2022 | CF Pachuca | - | Puebla FC | 1:0 | ||||
| 16. Round | 23/04/2022 | Puebla FC | - | Club Necaxa | 0:1 |  |
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