| 1. Round | 11/01/2021 | Santos Laguna | - | Cruz Azul | 1:0 | ||||
| 3. Round | 23/01/2021 | Mazatlán FC | - | Santos Laguna | 0:0 | ||||
| 4. Round | 01/02/2021 | Santos Laguna | - | CF América | 1:1 |  |
|||
| 5. Round | 06/02/2021 | Atlas Guadalajara | - | Santos Laguna | 1:1 | ||||
| 6. Round | 15/02/2021 | Santos Laguna | - | CF Monterrey | 1:0 | ||||
| 7. Round | 19/02/2021 | Atlético San Luis | - | Santos Laguna | 1:0 | ||||
| 10. Round | 08/03/2021 | Santos Laguna | - | Club Necaxa | 3:1 | ||||
| 11. Round | 14/03/2021 | Club Tijuana | - | Santos Laguna | 0:1 | ||||
| 13. Round | 04/04/2021 | Deportivo Guadalajara | - | Santos Laguna | 1:1 | ||||
| 14. Round | 12/04/2021 | Gallos Blancos | - | Santos Laguna | 1:0 | ||||
| 16. Round | 27/04/2021 | CF Pachuca | - | Santos Laguna | 1:0 | ||||
| 17. Round | 03/05/2021 | Santos Laguna | - | Puebla FC | 0:0 |
Mexico