| 3. Round | 23/01/2022 | Santos Laguna [U20] | - | Club Necaxa [U20] | 0:3 |  |
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| 5. Round | 12/02/2022 | Santos Laguna [U20] | - | CF América [U20] | 0:0 | ||||
| 6. Round | 18/02/2022 | FC Juárez [U20] | - | Santos Laguna [U20] | 1:2 | ||||
| 7. Round | 27/02/2022 | Cruz Azul [U20] | - | Santos Laguna [U20] | 2:1 | ||||
| 8. Round | 02/03/2022 | Santos Laguna [U20] | - | Pumas UNAM [U20] | 2:1 | ||||
| 9. Round | 05/03/2022 | Deportivo Guadalajara [U20] | - | Santos Laguna [U20] | 0:0 | ||||
| 10. Round | 12/03/2022 | Santos Laguna [U20] | - | Club Tijuana [U20] | 4:2 | ||||
| 11. Round | 18/03/2022 | Puebla FC [U20] | - | Santos Laguna [U20] | 0:1 | ||||
| 13. Round | 26/03/2022 | CF Monterrey [U20] | - | Santos Laguna [U20] | 1:2 |  |
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| 12. Round | 03/04/2022 | Santos Laguna [U20] | - | CF Pachuca [U20] | 1:0 | ||||
| 14. Round | 16/04/2022 | Santos Laguna [U20] | - | Gallos Blancos [U20] | 2:2 | ||||
| 15. Round | 19/04/2022 | Mazatlán FC [U20] | - | Santos Laguna [U20] | 1:2 | |
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| 16. Round | 24/04/2022 | Santos Laguna [U20] | - | Club León [U20] | 0:3 | ||||
| 17. Round | 01/05/2022 | Atlético San Luis [U20] | - | Santos Laguna [U20] | 2:2 |
Mexico