| 4. Round | 16/08/2021 | Santos Laguna | - | Deportivo Guadalajara | 0:0 | ||||
| 6. Round | 22/08/2021 | Club León | - | Santos Laguna | 1:1 | ||||
| 8. Round | 11/09/2021 | Club Tijuana | - | Santos Laguna | 2:1 | ||||
| 13. Round | 17/10/2021 | CF Pachuca | - | Santos Laguna | 1:1 | ||||
| 14. Round | 20/10/2021 | CF América | - | Santos Laguna | 2:1 | ||||
| 11. Round | 05/11/2021 | Pumas UNAM | - | Santos Laguna | 0:3 |
Mexico