| 2. Round | 01/08/2021 | Deportivo Toluca | - | UANL Tigres | 3:1 |  |
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| 3. Round | 07/08/2021 | Club Tijuana | - | Deportivo Toluca | 0:2 | ||||
| 4. Round | 15/08/2021 | Cruz Azul | - | Deportivo Toluca | 4:0 | ||||
| 5. Round | 17/08/2021 | Deportivo Toluca | - | Mazatlán FC | 2:2 | ||||
| 6. Round | 21/08/2021 | Atlas Guadalajara | - | Deportivo Toluca | 0:0 | ||||
| 7. Round | 29/08/2021 | Deportivo Toluca | - | Pumas UNAM | 2:1 | ||||
| 8. Round | 14/09/2021 | CF Pachuca | - | Deportivo Toluca | 1:2 | ||||
| 9. Round | 19/09/2021 | Deportivo Toluca | - | CF América | 3:1 | |
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| 11. Round | 23/09/2021 | CF Monterrey | - | Deportivo Toluca | 2:0 | ||||
| 10. Round | 26/09/2021 | Deportivo Toluca | - | Atlético San Luis | 1:2 | ||||
| 12. Round | 03/10/2021 | Deportivo Toluca | - | Gallos Blancos | 1:1 |  |
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| 13. Round | 17/10/2021 | Deportivo Guadalajara | - | Deportivo Toluca | 2:0 | ||||
| 14. Round | 21/10/2021 | Deportivo Toluca | - | Club Necaxa | 1:1 | ||||
| 15. Round | 25/10/2021 | Santos Laguna | - | Deportivo Toluca | 2:2 | ||||
| 17. Round | 06/11/2021 | Puebla FC | - | Deportivo Toluca | 1:0 |
Paraguay