| 1. Round | 09/01/2022 | Santos Laguna [] | - | CF Monterrey [] | 2:1 |  |
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| 3. Round | 22/01/2022 | UANL Tigres [] | - | Santos Laguna [] | 2:1 | ||||
| 4. Round | 29/01/2022 | Santos Laguna [] | - | Deportivo Guadalajara [] | 0:0 | ||||
| 5. Round | 04/02/2022 | Atlético San Luis [] | - | Santos Laguna [] | 0:2 | ||||
| 6. Round | 12/02/2022 | Santos Laguna [] | - | Atlas Guadalajara [] | 4:3 | ||||
| 7. Round | 18/02/2022 | Club León [] | - | Santos Laguna [] | 2:2 | ||||
| 8. Round | 26/02/2022 | Mazatlán FC [] | - | Santos Laguna [] | 0:3 | ||||
| 9. Round | 05/03/2022 | Santos Laguna [] | - | Club Tijuana [] | 2:1 | |
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| 10. Round | 12/03/2022 | Atlas Guadalajara [] | - | Santos Laguna [] | 3:0 | ||||
| 13. Round | 02/04/2022 | CF Monterrey [] | - | Santos Laguna [] | 2:0 | ||||
| 15. Round | 20/04/2022 | Club Tijuana [] | - | Santos Laguna [] | 4:1 | ||||
| 16. Round | 23/04/2022 | Santos Laguna [] | - | UANL Tigres [] | 5:0 | ||||
| 17. Round | 30/04/2022 | Deportivo Guadalajara [] | - | Santos Laguna [] | 4:0 | ||||
| 18. Round | 07/05/2022 | Santos Laguna [] | - | Club León [] | 2:3 |
Mexico