| 1. Round | 25/07/2021 | Deportivo Guadalajara | - | Atlético San Luis | 1:2 |  |
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| 2. Round | 03/08/2021 | Atlético San Luis | - | Gallos Blancos | 1:1 | ||||
| 3. Round | 08/08/2021 | Pumas UNAM | - | Atlético San Luis | 1:3 | ||||
| 4. Round | 13/08/2021 | Atlético San Luis | - | Club Necaxa | 0:2 | ||||
| 6. Round | 22/08/2021 | Atlético San Luis | - | Cruz Azul | 0:0 | ||||
| 7. Round | 28/08/2021 | Mazatlán FC | - | Atlético San Luis | 2:2 | ||||
| 8. Round | 11/09/2021 | Puebla FC | - | Atlético San Luis | 2:2 | |
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| 9. Round | 17/09/2021 | Atlético San Luis | - | Club Tijuana | 4:1 | ||||
| 14. Round | 22/09/2021 | FC Juárez | - | Atlético San Luis | 1:0 | ||||
| 11. Round | 29/09/2021 | Atlético San Luis | - | UANL Tigres | 0:3 | ||||
| 12. Round | 02/10/2021 | Club León | - | Atlético San Luis | 0:0 |
Paraguay