| 1. Round | 18/07/2021 | CF América [Women] | - | Santos Laguna [Women] | 2:1 |  |
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| 2. Round | 24/07/2021 | Mazatlán FC [Women] | - | Santos Laguna [Women] | 0:2 | ||||
| 3. Round | 03/08/2021 | Santos Laguna [Women] | - | Club Tijuana [Women] | 0:0 | ||||
| 6. Round | 24/08/2021 | Club León [Women] | - | Santos Laguna [Women] | 1:6 | ||||
| 8. Round | 05/09/2021 | Puebla FC [Women] | - | Santos Laguna [Women] | 2:3 | ||||
| 9. Round | 13/09/2021 | Santos Laguna [Women] | - | Deportivo Guadalajara [Women] | 5:4 | ||||
| 12. Round | 09/10/2021 | Deportivo Toluca [Women] | - | Santos Laguna [Women] | 1:0 | ||||
| 13. Round | 19/10/2021 | Santos Laguna [Women] | - | Pumas UNAM [Women] | 2:0 | ||||
| 14. Round | 02/11/2021 | Santos Laguna [Women] | - | Atlético San Luis [Women] | 3:1 | ||||
| 15. Round | 09/11/2021 | CF Pachuca [Women] | - | Santos Laguna [Women] | 4:0 | ||||
| 16. Round | 13/11/2021 | Gallos Blancos [Women] | - | Santos Laguna [Women] | 4:2 | ||||
| 17. Round | 22/11/2021 | Santos Laguna [Women] | - | UANL Tigres [Women] | 0:2 |
Mexico