| 1. Round | 19/07/2021 | Libertad | - | Guaireña FC | 0:0 | ||||
| 2. Round | 26/07/2021 | Cerro Porteño | - | Libertad | 1:1 | ||||
| 3. Round | 01/08/2021 | Libertad | - | Sol de América | 1:1 | ||||
| 4. Round | 07/08/2021 | Club Nacional | - | Libertad | 1:0 | ||||
| 6. Round | 24/08/2021 | Guaraní | - | Libertad | 2:2 |  |
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| 7. Round | 29/08/2021 | Libertad | - | Sportivo Luqueño | 5:0 | |
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| 11. Round | 04/10/2021 | Libertad | - | Cerro Porteño | 0:2 |  |
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| 12. Round | 17/10/2021 | Sol de América | - | Libertad | 0:4 | |
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| 13. Round | 25/10/2021 | Libertad | - | Club Nacional | 1:2 | ||||
| 14. Round | 30/10/2021 | 12 de Octubre de Itauguá | - | Libertad | 0:1 | ||||
| 15. Round | 07/11/2021 | Libertad | - | Guaraní | 2:0 | |
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| 16. Round | 20/11/2021 | Sportivo Luqueño | - | Libertad | 2:2 | ||||
| 17. Round | 26/11/2021 | Club Olimpia | - | Libertad | 2:3 | |
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| 18. Round | 03/12/2021 | Libertad | - | River Plate | 5:0 | |
Paraguay