| 1. Jornada | 24.07.2021 | Club Necaxa | - | Santos Laguna | 0:3 | ||||
| 2. Jornada | 02.08.2021 | Santos Laguna | - | Cruz Azul | 1:1 | ||||
| 3. Jornada | 08.08.2021 | UANL Tigres | - | Santos Laguna | 1:1 | ||||
| 6. Jornada | 22.08.2021 | Club León | - | Santos Laguna | 1:1 | ||||
| 7. Jornada | 30.08.2021 | Santos Laguna | - | FC Juárez | 2:0 | ||||
| 8. Jornada | 11.09.2021 | Club Tijuana | - | Santos Laguna | 2:1 | ||||
| 9. Jornada | 20.09.2021 | Santos Laguna | - | Puebla FC | 1:1 | ||||
| 10. Jornada | 27.09.2021 | Santos Laguna | - | CF Monterrey | 1:2 | ||||
| 12. Jornada | 03.10.2021 | Santos Laguna | - | Mazatlán FC | 1:0 | ||||
| 13. Jornada | 17.10.2021 | CF Pachuca | - | Santos Laguna | 1:1 | ||||
| 14. Jornada | 20.10.2021 | CF América | - | Santos Laguna | 2:1 |  |
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| 15. Jornada | 25.10.2021 | Santos Laguna | - | Deportivo Toluca | 2:2 | ||||
| 16. Jornada | 31.10.2021 | Gallos Blancos | - | Santos Laguna | 2:3 | |
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| 11. Jornada | 05.11.2021 | Pumas UNAM | - | Santos Laguna | 0:3 |  |
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| 17. Jornada | 08.11.2021 | Santos Laguna | - | Atlético San Luis | 0:0 |
México