| 1. Round | 10/01/2021 | CF América | - | Atlético San Luis | 2:1 | ||||
| 2. Round | 16/01/2021 | Club Necaxa | - | Atlético San Luis | 1:0 |  |
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| 3. Round | 22/01/2021 | Atlético San Luis | - | Deportivo Guadalajara | 3:1 |  |
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| 4. Round | 02/02/2021 | Club León | - | Atlético San Luis | 3:1 | ||||
| 5. Round | 05/02/2021 | Atlético San Luis | - | Club Tijuana | 2:2 | ||||
| 6. Round | 13/02/2021 | Mazatlán FC | - | Atlético San Luis | 0:3 | ||||
| 7. Round | 19/02/2021 | Atlético San Luis | - | Santos Laguna | 1:0 | |
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| 8. Round | 26/02/2021 | Atlético San Luis | - | UANL Tigres | 2:2 | |
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| 9. Round | 02/03/2021 | Atlas Guadalajara | - | Atlético San Luis | 3:1 | ||||
| 10. Round | 06/03/2021 | Atlético San Luis | - | Deportivo Toluca | 0:0 | ||||
| 11. Round | 15/03/2021 | Gallos Blancos | - | Atlético San Luis | 2:1 | ||||
| 12. Round | 20/03/2021 | Atlético San Luis | - | Pumas UNAM | 0:1 | ||||
| 13. Round | 04/04/2021 | CF Monterrey | - | Atlético San Luis | 2:0 | |
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| 14. Round | 10/04/2021 | FC Juárez | - | Atlético San Luis | 2:1 | ||||
| 15. Round | 17/04/2021 | Atlético San Luis | - | Puebla FC | 1:4 | |
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| 16. Round | 24/04/2021 | Cruz Azul | - | Atlético San Luis | 3:2 | ||||
| 17. Round | 30/04/2021 | Atlético San Luis | - | CF Pachuca | 1:5 | |
Argentina
Chile