| 1. Round | 04/07/2022 | Santos Laguna | - | CF Monterrey | 4:3 |  |
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| 2. Round | 09/07/2022 | Puebla FC | - | Santos Laguna | 1:0 | ||||
| 3. Round | 17/07/2022 | Santos Laguna | - | Deportivo Guadalajara | 1:1 | ||||
| 4. Round | 23/07/2022 | Deportivo Toluca | - | Santos Laguna | 2:1 | ||||
| 6. Round | 01/08/2022 | Santos Laguna | - | Atlas Guadalajara | 1:0 |  |
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| 7. Round | 07/08/2022 | Santos Laguna | - | Cruz Azul | 4:0 | ||||
| 8. Round | 15/08/2022 | UANL Tigres | - | Santos Laguna | 2:0 | |
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| 9. Round | 19/08/2022 | Santos Laguna | - | Club León | 2:1 | |
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| 10. Round | 21/08/2022 | Pumas UNAM | - | Santos Laguna | 1:5 | ||||
| 16. Round | 26/08/2022 | Club Tijuana | - | Santos Laguna | 0:2 | ||||
| 11. Round | 29/08/2022 | Santos Laguna | - | Atlético San Luis | 4:1 | ||||
| 15. Round | 19/09/2022 | Santos Laguna | - | FC Juárez | 2:0 | ||||
| 17. Round | 03/10/2022 | Santos Laguna | - | Mazatlán FC | 3:0 |
Ecuador