| 4. Round | 20/02/2021 | Guaraní | - | Club Olimpia | 0:3 | ||||
| 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 |  |
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| 11. Round | 13/04/2021 | Guaraní | - | River Plate | 2:0 | |
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| 12. Round | 17/04/2021 | 12 de Octubre de Itauguá | - | Guaraní | 1:1 | |
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| 13. Round | 25/04/2021 | Club Olimpia | - | Guaraní | 2:1 | ||||
| 15. Round | 08/05/2021 | Sportivo Luqueño | - | Guaraní | 1:2 | ||||
| 16. Round | 17/05/2021 | Guaraní | - | Libertad | 1:6 | ||||
| 18. Round | 29/05/2021 | Guaraní | - | Cerro Porteño | 2:0 |
Uruguay