| 1. Round | 17/07/2021 | Sportivo Luqueño | - | Cerro Porteño | 0:0 | ||||
| 2. Round | 26/07/2021 | Cerro Porteño | - | Libertad | 1:1 | ||||
| 3. Round | 31/07/2021 | River Plate | - | Cerro Porteño | 0:0 | ||||
| 4. Round | 08/08/2021 | Cerro Porteño | - | Guaireña FC | 2:0 | ||||
| 5. Round | 14/08/2021 | Club Olimpia | - | Cerro Porteño | 0:3 |  |
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| 6. Round | 22/08/2021 | Sol de América | - | Cerro Porteño | 1:2 | ||||
| 7. Round | 29/08/2021 | Cerro Porteño | - | Club Nacional | 0:2 | ||||
| 9. Round | 19/09/2021 | Cerro Porteño | - | Guaraní | 0:0 | |
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| 10. Round | 26/09/2021 | Cerro Porteño | - | Sportivo Luqueño | 0:1 | ||||
| 11. Round | 04/10/2021 | Libertad | - | Cerro Porteño | 0:2 | ||||
| 12. Round | 19/10/2021 | Cerro Porteño | - | River Plate | 2:0 | ||||
| 14. Round | 31/10/2021 | Cerro Porteño | - | Club Olimpia | 1:0 | ||||
| 16. Round | 21/11/2021 | Club Nacional | - | Cerro Porteño | 1:5 | ||||
| 17. Round | 28/11/2021 | Cerro Porteño | - | 12 de Octubre de Itauguá | 1:0 | ||||
| 18. Round | 04/12/2021 | Guaraní | - | Cerro Porteño | 2:2 |
Paraguay