| 1. Round | 18/07/2016 | Santos Laguna | - | UANL Tigres | 0:0 |  |
|||
| 4. Round | 08/08/2016 | Puebla FC | - | Santos Laguna | 0:0 | ||||
| 5. Round | 15/08/2016 | Santos Laguna | - | Deportivo Guadalajara | 0:1 | |
|||
| 6. Round | 20/08/2016 | Cruz Azul | - | Santos Laguna | 3:1 | |
|||
| 7. Round | 29/08/2016 | Santos Laguna | - | Club León | 1:0 | |
|||
| 8. Round | 11/09/2016 | Club Necaxa | - | Santos Laguna | 2:1 | ||||
| 9. Round | 19/09/2016 | Santos Laguna | - | Pumas UNAM | 3:1 | |
|||
| 11. Round | 26/09/2016 | Santos Laguna | - | Club Tijuana | 1:2 | ||||
| 12. Round | 01/10/2016 | Gallos Blancos | - | Santos Laguna | 1:1 | ||||
| 13. Round | 16/10/2016 | CF Pachuca | - | Santos Laguna | 3:0 | ||||
| 14. Round | 24/10/2016 | Santos Laguna | - | Atlas Guadalajara | 2:2 | ||||
| 15. Round | 30/10/2016 | CF América | - | Santos Laguna | 3:1 | ||||
| 16. Round | 07/11/2016 | Santos Laguna | - | Chiapas FC | 2:0 | ||||
| 17. Round | 20/11/2016 | Deportivo Toluca | - | Santos Laguna | 1:2 |
Colombia