| 2. Round | 13/02/2022 | Guaraní | - | Sol de América | 0:1 | ||||
| 3. Round | 19/02/2022 | Cerro Porteño | - | Guaraní | 2:0 | ||||
| 5. Round | 07/03/2022 | 12 de Octubre de Itauguá | - | Guaraní | 1:3 | ||||
| 6. Round | 12/03/2022 | Guaraní | - | General Caballero DJLM | 3:1 | ||||
| 7. Round | 20/03/2022 | Libertad | - | Guaraní | 2:0 | ||||
| 8. Round | 04/04/2022 | Guaraní | - | Tacuary | 1:2 | ||||
| 10. Round | 17/04/2022 | Guaraní | - | Club Nacional | 0:1 | ||||
| 11. Round | 20/04/2022 | Club Olimpia | - | Guaraní | 1:0 | ||||
| 12. Round | 25/04/2022 | Guaraní | - | Guaireña FC | 2:1 |  |
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| 13. Round | 01/05/2022 | Sol de América | - | Guaraní | 2:2 | ||||
| 14. Round | 09/05/2022 | Guaraní | - | Cerro Porteño | 1:2 | ||||
| 15. Round | 12/05/2022 | Resistencia SC | - | Guaraní | 1:2 | ||||
| 16. Round | 17/05/2022 | Guaraní | - | 12 de Octubre de Itauguá | 3:0 | ||||
| 17. Round | 22/05/2022 | General Caballero DJLM | - | Guaraní | 0:4 | ||||
| 18. Round | 14/06/2022 | Guaraní | - | Libertad | 1:1 |  |
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| 19. Round | 19/06/2022 | Tacuary | - | Guaraní | 0:2 | ||||
| 20. Round | 23/06/2022 | Guaraní | - | Sportivo Ameliano | 1:1 | ||||
| 21. Round | 26/06/2022 | Club Nacional | - | Guaraní | 0:1 | ||||
| 22. Round | 03/07/2022 | Guaraní | - | Club Olimpia | 0:2 |
Paraguay