| 1. Jornada | 11.01.2021 | Santos Laguna | - | Cruz Azul | 1:0 | ||||
| 2. Jornada | 18.01.2021 | Santos Laguna | - | UANL Tigres | 2:0 | ||||
| 3. Jornada | 23.01.2021 | Mazatlán FC | - | Santos Laguna | 0:0 |  |
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| 4. Jornada | 01.02.2021 | Santos Laguna | - | CF América | 1:1 | ||||
| 5. Jornada | 07.02.2021 | Atlas Guadalajara | - | Santos Laguna | 1:1 | ||||
| 6. Jornada | 15.02.2021 | Santos Laguna | - | CF Monterrey | 1:0 | ||||
| 7. Jornada | 19.02.2021 | Atlético San Luis | - | Santos Laguna | 1:0 | ||||
| 8. Jornada | 01.03.2021 | Santos Laguna | - | FC Juárez | 3:2 | ||||
| 9. Jornada | 05.03.2021 | Pumas UNAM | - | Santos Laguna | 1:0 | ||||
| 10. Jornada | 08.03.2021 | Santos Laguna | - | Club Necaxa | 3:1 |  |
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| 11. Jornada | 14.03.2021 | Club Tijuana | - | Santos Laguna | 0:1 | ||||
| 12. Jornada | 22.03.2021 | Santos Laguna | - | Club León | 1:2 | |
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| 16. Jornada | 27.04.2021 | CF Pachuca | - | Santos Laguna | 1:0 | ||||
| 17. Jornada | 03.05.2021 | Santos Laguna | - | Puebla FC | 0:0 |
Uruguay
