| 6. Round | 01/08/2022 | Santos Laguna | - | Atlas Guadalajara | 1:0 | ||||
| 7. Round | 07/08/2022 | Santos Laguna | - | Cruz Azul | 4:0 | ||||
| 8. Round | 15/08/2022 | UANL Tigres | - | Santos Laguna | 2:0 | ||||
| 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 | ||||
| 12. Round | 03/09/2022 | CF Pachuca | - | Santos Laguna | 2:0 | ||||
| 13. Round | 07/09/2022 | Santos Laguna | - | Club Necaxa | 3:1 | ||||
| 14. Round | 10/09/2022 | Gallos Blancos | - | Santos Laguna | 3:3 | ||||
| 5. Round | 15/09/2022 | CF América | - | Santos Laguna | 3:3 | ||||
| 17. Round | 03/10/2022 | Santos Laguna | - | Mazatlán FC | 3:0 |
Paraguay