| 1. Round | 05/02/2021 | Guaraní | - | Club Nacional | 2:2 |  |
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| 2. Round | 09/02/2021 | River Plate | - | Guaraní | 1:4 | ||||
| 3. Round | 13/02/2021 | Guaraní | - | 12 de Octubre de Itauguá | 2:1 |  |
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| 4. Round | 20/02/2021 | Guaraní | - | Club Olimpia | 0:3 | ||||
| 5. Round | 27/02/2021 | Sol de América | - | Guaraní | 1:3 | |
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| 6. Round | 07/03/2021 | Guaraní | - | Sportivo Luqueño | 0:1 | ||||
| 8. Round | 14/03/2021 | Guaraní | - | Guaireña FC | 0:3 | ||||
| 9. Round | 21/03/2021 | Cerro Porteño | - | Guaraní | 2:1 | ||||
| 7. Round | 29/03/2021 | Libertad | - | Guaraní | 1:1 | ||||
| 11. Round | 13/04/2021 | Guaraní | - | River Plate | 2:0 | ||||
| 12. Round | 17/04/2021 | 12 de Octubre de Itauguá | - | Guaraní | 1:1 | ||||
| 13. Round | 25/04/2021 | Club Olimpia | - | Guaraní | 2:1 | ||||
| 14. Round | 02/05/2021 | Guaraní | - | Sol de América | 2:0 | ||||
| 15. Round | 08/05/2021 | Sportivo Luqueño | - | Guaraní | 1:2 | ||||
| 17. Round | 22/05/2021 | Guaireña FC | - | Guaraní | 0:0 | ||||
| 18. Round | 29/05/2021 | Guaraní | - | Cerro Porteño | 2:0 |
Paraguay