| 1. Round | 23/07/2021 | Club Necaxa [U18] | - | Santos Laguna [U18] | 3:1 |  |
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| 3. Round | 07/08/2021 | UANL Tigres [U18] | - | Santos Laguna [U18] | 0:0 | ||||
| 4. Round | 15/08/2021 | Santos Laguna [U18] | - | Deportivo Guadalajara [U18] | 1:1 | ||||
| 5. Round | 18/08/2021 | Santos Laguna [U18] | - | Atlas Guadalajara [U18] | 2:3 | ||||
| 6. Round | 21/08/2021 | Club León [U18] | - | Santos Laguna [U18] | 3:1 |  |
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| 7. Round | 29/08/2021 | Santos Laguna [U18] | - | FC Juárez [U18] | 0:0 | ||||
| 8. Round | 10/09/2021 | Club Tijuana [U18] | - | Santos Laguna [U18] | 3:0 | ||||
| 12. Round | 02/10/2021 | Santos Laguna [U18] | - | Mazatlán FC [U18] | 3:0 | ||||
| 13. Round | 16/10/2021 | CF Pachuca [U18] | - | Santos Laguna [U18] | 0:1 | ||||
| 15. Round | 24/10/2021 | Santos Laguna [U18] | - | Deportivo Toluca [U18] | 3:1 | ||||
| 16. Round | 30/10/2021 | Gallos Blancos [U18] | - | Santos Laguna [U18] | 1:1 | ||||
| 11. Round | 04/11/2021 | Pumas UNAM [U18] | - | Santos Laguna [U18] | 0:1 |
Mexico