| 2. Round | 16/01/2022 | Deportivo Toluca [U18] | - | Santos Laguna [U18] | 2:2 | ||||
| 3. Round | 23/01/2022 | Santos Laguna [U18] | - | Club Necaxa [U18] | 1:2 | ||||
| 5. Round | 12/02/2022 | Santos Laguna [U18] | - | CF América [U18] | 2:2 | ||||
| 6. Round | 18/02/2022 | FC Juárez [U18] | - | Santos Laguna [U18] | 0:1 | ||||
| 8. Round | 02/03/2022 | Santos Laguna [U18] | - | Pumas UNAM [U18] | 0:0 | ||||
| 9. Round | 05/03/2022 | Deportivo Guadalajara [U18] | - | Santos Laguna [U18] | 1:1 | ||||
| 10. Round | 12/03/2022 | Santos Laguna [U18] | - | Club Tijuana [U18] | 4:0 | ||||
| 11. Round | 18/03/2022 | Puebla FC [U18] | - | Santos Laguna [U18] | 2:2 |  |
|||
| 13. Round | 26/03/2022 | CF Monterrey [U18] | - | Santos Laguna [U18] | 1:2 | ||||
| 12. Round | 03/04/2022 | Santos Laguna [U18] | - | CF Pachuca [U18] | 3:1 | ||||
| 16. Round | 24/04/2022 | Santos Laguna [U18] | - | Club León [U18] | 2:3 | ||||
| 17. Round | 01/05/2022 | Atlético San Luis [U18] | - | Santos Laguna [U18] | 0:1 |
Mexico