| 1. Ronde | 11.01.2021 | Santos Laguna | - | Cruz Azul | 1:0 |  |
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| 2. Ronde | 18.01.2021 | Santos Laguna | - | UANL Tigres | 2:0 | ||||
| 3. Ronde | 23.01.2021 | Mazatlán FC | - | Santos Laguna | 0:0 | ||||
| 4. Ronde | 01.02.2021 | Santos Laguna | - | CF América | 1:1 | ||||
| 5. Ronde | 07.02.2021 | Atlas Guadalajara | - | Santos Laguna | 1:1 | |
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| 6. Ronde | 15.02.2021 | Santos Laguna | - | CF Monterrey | 1:0 | ||||
| 7. Ronde | 19.02.2021 | Atlético San Luis | - | Santos Laguna | 1:0 |  |
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| 10. Ronde | 08.03.2021 | Santos Laguna | - | Club Necaxa | 3:1 | ||||
| 11. Ronde | 14.03.2021 | Club Tijuana | - | Santos Laguna | 0:1 |  |
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| 12. Ronde | 22.03.2021 | Santos Laguna | - | Club León | 1:2 | |
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| 13. Ronde | 05.04.2021 | Deportivo Guadalajara | - | Santos Laguna | 1:1 | ||||
| 14. Ronde | 12.04.2021 | Gallos Blancos | - | Santos Laguna | 1:0 | ||||
| 15. Ronde | 19.04.2021 | Santos Laguna | - | Deportivo Toluca | 3:1 | ||||
| 16. Ronde | 27.04.2021 | CF Pachuca | - | Santos Laguna | 1:0 | ||||
| 17. Ronde | 03.05.2021 | Santos Laguna | - | Puebla FC | 0:0 | |
Ecuador