| 5. Round | 21/08/2021 | Santos Laguna [U16] | - | Atlético San Luis [U16] | 2:0 | ||||
| 6. Round | 28/08/2021 | Atlas Guadalajara [U16] | - | Santos Laguna [U16] | 1:5 |  |
|||
| 7. Round | 04/09/2021 | Santos Laguna [U16] | - | Club León [U16] | 1:0 |  |
|||
| 8. Round | 11/09/2021 | Santos Laguna [U16] | - | Mazatlán FC [U16] | 4:2 | ||||
| 9. Round | 18/09/2021 | Club Necaxa [U16] | - | Santos Laguna [U16] | 1:1 | |
|||
| 10. Round | 25/09/2021 | Santos Laguna [U16] | - | Atlas Guadalajara [U16] | 1:2 | ||||
| 11. Round | 02/10/2021 | Atlético San Luis [U16] | - | Santos Laguna [U16] | 0:3 | ||||
| 12. Round | 09/10/2021 | Mazatlán FC [U16] | - | Santos Laguna [U16] | 1:2 | ||||
| 13. Round | 16/10/2021 | Santos Laguna [U16] | - | CF Monterrey [U16] | 1:1 | ||||
| 15. Round | 30/10/2021 | Santos Laguna [U16] | - | Club Necaxa [U16] | 2:1 | |
|||
| 16. Round | 06/11/2021 | UANL Tigres [U16] | - | Santos Laguna [U16] | 4:0 | ||||
| 18. Round | 20/11/2021 | Club León [U16] | - | Santos Laguna [U16] | 0:1 |
Mexico