| 3. Round | 07/08/2021 | Club Necaxa | - | Cruz Azul | 1:2 | ||||
| 4. Round | 15/08/2021 | Cruz Azul | - | Deportivo Toluca | 4:0 | ||||
| 5. Round | 19/08/2021 | Cruz Azul | - | CF Monterrey | 1:1 |  |
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| 6. Round | 22/08/2021 | Atlético San Luis | - | Cruz Azul | 0:0 | ||||
| 7. Round | 30/08/2021 | Cruz Azul | - | CF Pachuca | 1:1 |  |
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| 10. Round | 25/09/2021 | Puebla FC | - | Cruz Azul | 1:1 | ||||
| 12. Round | 04/10/2021 | Club Tijuana | - | Cruz Azul | 0:1 | ||||
| 13. Round | 17/10/2021 | Cruz Azul | - | UANL Tigres | 1:1 | ||||
| 14. Round | 20/10/2021 | Atlas Guadalajara | - | Cruz Azul | 0:0 | ||||
| 15. Round | 24/10/2021 | Deportivo Guadalajara | - | Cruz Azul | 1:1 | |
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| 16. Round | 31/10/2021 | Cruz Azul | - | CF América | 2:1 | |
Uruguay