| 5. Ronde | 13.02.2022 | Santos Laguna | - | CF América | 2:3 |  |
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| 2. Ronde | 17.02.2022 | Mazatlán FC | - | CF América | 2:1 | ||||
| 6. Ronde | 20.02.2022 | CF América | - | CF Pachuca | 1:3 | |
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| 7. Ronde | 27.02.2022 | Pumas UNAM | - | CF América | 0:0 | |
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| 8. Ronde | 02.03.2022 | CF América | - | Gallos Blancos | 1:1 | |
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| 9. Ronde | 06.03.2022 | CF Monterrey | - | CF América | 2:1 | ||||
| 10. Ronde | 13.03.2022 | Deportivo Guadalajara | - | CF América | 0:0 | ||||
| 11. Ronde | 21.03.2022 | CF América | - | Deportivo Toluca | 3:0 | ||||
| 12. Ronde | 03.04.2022 | Club Necaxa | - | CF América | 0:1 | |
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| 14. Ronde | 16.04.2022 | Club Tijuana | - | CF América | 1:3 | ||||
| 16. Ronde | 24.04.2022 | UANL Tigres | - | CF América | 0:2 | ||||
| 17. Ronde | 01.05.2022 | CF América | - | Cruz Azul | 0:0 |
Paraguay