| 2. Round | 15/01/2022 | Atlas Guadalajara | - | Atlético San Luis | 1:0 | ||||
| 3. Round | 21/01/2022 | Atlético San Luis | - | FC Juárez | 0:1 | ||||
| 4. Round | 06/02/2022 | CF América | - | Atlético San Luis | 2:3 |  |
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| 5. Round | 12/02/2022 | Atlético San Luis | - | Deportivo Toluca | 0:1 | ||||
| 6. Round | 20/02/2022 | UANL Tigres | - | Atlético San Luis | 2:1 | ||||
| 7. Round | 26/02/2022 | CF Monterrey | - | Atlético San Luis | 0:2 | |
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| 8. Round | 03/03/2022 | Atlético San Luis | - | Deportivo Guadalajara | 2:2 | ||||
| 10. Round | 13/03/2022 | Atlético San Luis | - | Puebla FC | 2:1 | ||||
| 11. Round | 18/03/2022 | Gallos Blancos | - | Atlético San Luis | 2:1 | ||||
| 9. Round | 07/04/2022 | Club Tijuana | - | Atlético San Luis | 1:1 | ||||
| 13. Round | 09/04/2022 | Atlético San Luis | - | Club León | 2:0 | ||||
| 14. Round | 16/04/2022 | Club Necaxa | - | Atlético San Luis | 4:2 | ||||
| 15. Round | 21/04/2022 | Atlético San Luis | - | Pumas UNAM | 2:0 | ||||
| 16. Round | 24/04/2022 | Cruz Azul | - | Atlético San Luis | 0:1 | ||||
| 17. Round | 01/05/2022 | Atlético San Luis | - | Santos Laguna | 1:3 |
Uruguay
