| 08 Feb 22 | Qualifier     | Deportivo LaraDeportivo Lar | 2 - 3 | BolivarBolivar |
| 09 Feb 22 | Qualifier | Montevideo City TorqueMontevideo Ci | 1 - 1 | Barcelona SCBarcelona SC |
| 10 Feb 22 | Qualifier | Universidad César VallejoUniversidad C | 0 - 1 | Club OlimpiaClub Olimpia |
| 15 Feb 22 | Qualifier  | BolivarBolivar | 4 - 0 | Deportivo LaraDeportivo Lar |
| 16 Feb 22 | Qualifier | Barcelona SCBarcelona SC | 0 - 0 | Montevideo City TorqueMontevideo Ci |
| 17 Feb 22 | Qualifier | Club OlimpiaClub Olimpia | 2 - 0 | Universidad César VallejoUniversidad C |
| 21 Feb 22 | Qualifier | Everton de Viña del MarEverton de Vi | 3 - 0 | Monagas S.C.Monagas S.C. |
| 22 Feb 22 | Qualifier | America MGAmerica MG | 0 - 1 | Club GuaraníClub Guaraní |
| 22 Feb 22 | Qualifier | BolivarBolivar | 1 - 1 | Universidad Católica del Universidad C |
| 23 Feb 22 | Qualifier | Plaza ColoniaPlaza Colonia | 2 - 0 | The StrongestThe Strongest |
| 23 Feb 22 | Qualifier | Millonarios F.C.Millonarios F | 1 - 2 | FluminenseFluminense |
| 24 Feb 22 | Qualifier | Audax ItalianoAudax Italian | 1 - 0 | Estudiantes de la PlataEstudiantes d |
| 24 Feb 22 | Qualifier | Barcelona SCBarcelona SC | 2 - 0 | UniversitarioUniversitario |
| 25 Feb 22 | Qualifier | Club OlimpiaClub Olimpia | 3 - 1 | Atlético NacionalAtlético Naci |
| 28 Feb 22 | Qualifier | Monagas S.C.Monagas S.C. | 1 - 0 | Everton de Viña del MarEverton de Vi |
| 01 Mar 22 | Qualifier | Club GuaraníClub Guaraní | 2 - 3 | America MGAmerica MG |
| 01 Mar 22 | Qualifier | Universidad Católica del Universidad C | 2 - 0 | BolivarBolivar |
| 02 Mar 22 | Qualifier | The StrongestThe Strongest | 3 - 0 | Plaza ColoniaPlaza Colonia |
| 02 Mar 22 | Qualifier | FluminenseFluminense | 2 - 0 | Millonarios F.C.Millonarios F |
| 03 Mar 22 | Qualifier | Estudiantes de la PlataEstudiantes d | 2 - 0 | Audax ItalianoAudax Italian |
| 03 Mar 22 | Qualifier | UniversitarioUniversitario | 0 - 1 | Barcelona SCBarcelona SC |
| 04 Mar 22 | Qualifier | Atlético NacionalAtlético Naci | 1 - 1 | Club OlimpiaClub Olimpia |
| 08 Mar 22 | Qualifier | Everton de Viña del MarEverton de Vi | 0 - 1 | Estudiantes de la PlataEstudiantes d |
| 09 Mar 22 | Qualifier | America MGAmerica MG | 0 - 0 | Barcelona SCBarcelona SC |
| 10 Mar 22 | Qualifier | FluminenseFluminense | 3 - 1 | Club OlimpiaClub Olimpia |
| 11 Mar 22 | Qualifier | Universidad Católica del Universidad C | 0 - 0 | The StrongestThe Strongest |
| 15 Mar 22 | Qualifier | Estudiantes de la PlataEstudiantes d | 1 - 0 | Everton de Viña del MarEverton de Vi |
| 16 Mar 22 | Qualifier | Barcelona SCBarcelona SC | 0 - 0 | America MGAmerica MG |
| 17 Mar 22 | Qualifier | Club OlimpiaClub Olimpia | 2 - 0 | FluminenseFluminense |
| 18 Mar 22 | Qualifier | The StrongestThe Strongest | 2 - 1 | Universidad Católica del Universidad C |
| |
| 05 Apr 22 | r01 | Caracas F.C.Caracas F.C. | 0 - 0 | Atletico PRAtletico PR |
| 05 Apr 22 | r01 | Club OlimpiaClub Olimpia | 0 - 0 | Cerro PorteñoCerro Porteño |
| 05 Apr 22 | r01 | ColonColon | 2 - 1 | PeñarolPeñarol |
| 06 Apr 22 | r01 | Always ReadyAlways Ready | 2 - 0 | CorinthiansCorinthians |
| 06 Apr 22 | r01 | Deportivo CaliDeportivo Cal | 2 - 0 | Boca JuniorsBoca Juniors |
| 06 Apr 22 | r01 | Sporting CristalSporting Cris | 0 - 2 | FlamengoFlamengo |
| 06 Apr 22 | r01 | BragantinoBragantino | 2 - 0 | Nacional MontevideoNacional Mont |
| 06 Apr 22 | r01 | America MGAmerica MG | 0 - 2 | Independiente del ValleIndependiente |
| 06 Apr 22 | r01 | Talleres de CordobaTalleres de C | 1 - 0 | Universidad CatólicaUniversidad C |
| 07 Apr 22 | r01 | Deportivo Táchira F.C.Deportivo Tác | 0 - 4 | PalmeirasPalmeiras |
| 07 Apr 22 | r01 | Deportes TolimaDeportes Toli | 0 - 2 | Atletico MGAtletico MG |
| 07 Apr 22 | r01 | Alianza LimaAlianza Lima | 0 - 1 | River PlateRiver Plate |
| 07 Apr 22 | r01 | Independiente PetroleroIndependiente | 1 - 1 | EmelecEmelec |
| 07 Apr 22 | r01 | FortalezaFortaleza | 1 - 2 | Colo-ColoColo-Colo |
| 08 Apr 22 | r01 | Estudiantes de la PlataEstudiantes d | 4 - 1 | Velez SarsfieldVelez Sarsfie |
| 08 Apr 22 | r01 | The StrongestThe Strongest | 1 - 1 | Club LibertadClub Libertad |
| |
| 12 Apr 22 | r02 | Boca JuniorsBoca Juniors | 2 - 0 | Always ReadyAlways Ready |
| 12 Apr 22 | r02 | Cerro PorteñoCerro Porteño | 3 - 1 | ColonColon |
| 12 Apr 22 | r02 | Universidad CatólicaUniversidad C | 2 - 1 | Sporting CristalSporting Cris |
| 13 Apr 22 | r02 | PalmeirasPalmeiras | 8 - 1 | Independiente PetroleroIndependiente |
| 13 Apr 22 | r02 | PeñarolPeñarol | 2 - 1 | Club OlimpiaClub Olimpia |
| 13 Apr 22 | r02 | FlamengoFlamengo | 3 - 1 | Talleres de CordobaTalleres de C |
| 13 Apr 22 | r02 | Club LibertadClub Libertad | 2 - 1 | Caracas F.C.Caracas F.C. |
| 13 Apr 22 | r02 | Colo-ColoColo-Colo | 2 - 1 | Alianza LimaAlianza Lima |
| 14 Apr 22 | r02 | River PlateRiver Plate | 2 - 0 | FortalezaFortaleza |
| 14 Apr 22 | r02 | Nacional MontevideoNacional Mont | 0 - 0 | Estudiantes de la PlataEstudiantes d |
| 14 Apr 22 | r02 | Atletico MGAtletico MG | 1 - 1 | America MGAmerica MG |
| 14 Apr 22 | r02 | CorinthiansCorinthians | 1 - 0 | Deportivo CaliDeportivo Cal |
| 14 Apr 22 | r02 | Independiente del ValleIndependiente | 2 - 2 | Deportes TolimaDeportes Toli |
| 14 Apr 22 | r02 | Atletico PRAtletico PR | 1 - 0 | The StrongestThe Strongest |
| 15 Apr 22 | r02 | Velez SarsfieldVelez Sarsfie | 2 - 2 | BragantinoBragantino |
| 15 Apr 22 | r02 | EmelecEmelec | 1 - 1 | Deportivo Táchira F.C.Deportivo Tác |
| |
| 26 Apr 22 | r03 | Independiente PetroleroIndependiente | 1 - 2 | Deportivo Táchira F.C.Deportivo Tác |
| 26 Apr 22 | r03 | Club LibertadClub Libertad | 1 - 0 | Atletico PRAtletico PR |
| 26 Apr 22 | r03 | Velez SarsfieldVelez Sarsfie | 1 - 2 | Nacional MontevideoNacional Mont |
| 26 Apr 22 | r03 | Estudiantes de la PlataEstudiantes d | 2 - 0 | BragantinoBragantino |
| 27 Apr 22 | r03 | Independiente del ValleIndependiente | 1 - 1 | Atletico MGAtletico MG |
| 27 Apr 22 | r03 | CorinthiansCorinthians | 2 - 0 | Boca JuniorsBoca Juniors |
| 27 Apr 22 | r03 | Talleres de CordobaTalleres de C | 1 - 0 | Sporting CristalSporting Cris |
| 27 Apr 22 | r03 | America MGAmerica MG | 2 - 3 | Deportes TolimaDeportes Toli |
| 27 Apr 22 | r03 | FortalezaFortaleza | 2 - 1 | Alianza LimaAlianza Lima |
| 28 Apr 22 | r03 | Cerro PorteñoCerro Porteño | 1 - 0 | PeñarolPeñarol |
| 28 Apr 22 | r03 | EmelecEmelec | 1 - 3 | PalmeirasPalmeiras |
| 28 Apr 22 | r03 | Colo-ColoColo-Colo | 1 - 2 | River PlateRiver Plate |
| 28 Apr 22 | r03 | The StrongestThe Strongest | 1 - 1 | Caracas F.C.Caracas F.C. |
| 28 Apr 22 | r03 | Universidad CatólicaUniversidad C | 2 - 3 | FlamengoFlamengo |
| 29 Apr 22 | r03 | Club OlimpiaClub Olimpia | 0 - 0 | ColonColon |
| 29 Apr 22 | r03 | Always ReadyAlways Ready | 2 - 2 | Deportivo CaliDeportivo Cal |
| |
| 03 May 22 | r04 | Deportivo Táchira F.C.Deportivo Tác | 1 - 4 | EmelecEmelec |
| 03 May 22 | r04 | Caracas F.C.Caracas F.C. | 1 - 0 | Club LibertadClub Libertad |
| 03 May 22 | r04 | The StrongestThe Strongest | 5 - 0 | Atletico PRAtletico PR |
| 04 May 22 | r04 | Independiente PetroleroIndependiente | 0 - 5 | PalmeirasPalmeiras |
| 04 May 22 | r04 | Estudiantes de la PlataEstudiantes d | 1 - 0 | Nacional MontevideoNacional Mont |
| 04 May 22 | r04 | America MGAmerica MG | 1 - 2 | Atletico MGAtletico MG |
| 04 May 22 | r04 | ColonColon | 2 - 1 | Cerro PorteñoCerro Porteño |
| 04 May 22 | r04 | Talleres de CordobaTalleres de C | 2 - 2 | FlamengoFlamengo |
| 05 May 22 | r04 | Deportivo CaliDeportivo Cal | 0 - 0 | CorinthiansCorinthians |
| 05 May 22 | r04 | Always ReadyAlways Ready | 0 - 1 | Boca JuniorsBoca Juniors |
| 05 May 22 | r04 | Club OlimpiaClub Olimpia | 1 - 0 | PeñarolPeñarol |
| 05 May 22 | r04 | Deportes TolimaDeportes Toli | 1 - 0 | Independiente del ValleIndependiente |
| 05 May 22 | r04 | Sporting CristalSporting Cris | 1 - 1 | Universidad CatólicaUniversidad C |
| 05 May 22 | r04 | FortalezaFortaleza | 1 - 1 | River PlateRiver Plate |
| 06 May 22 | r04 | BragantinoBragantino | 1 - 1 | Velez SarsfieldVelez Sarsfie |
| 06 May 22 | r04 | Alianza LimaAlianza Lima | 1 - 1 | Colo-ColoColo-Colo |
| |
| 17 May 22 | r05 | Caracas F.C.Caracas F.C. | 0 - 0 | The StrongestThe Strongest |
| 17 May 22 | r05 | BragantinoBragantino | 0 - 1 | Estudiantes de la PlataEstudiantes d |
| 17 May 22 | r05 | PeñarolPeñarol | 0 - 0 | Cerro PorteñoCerro Porteño |
| 18 May 22 | r05 | Boca JuniorsBoca Juniors | 1 - 1 | CorinthiansCorinthians |
| 18 May 22 | r05 | FlamengoFlamengo | 3 - 0 | Universidad CatólicaUniversidad C |
| 18 May 22 | r05 | Sporting CristalSporting Cris | 0 - 0 | Talleres de CordobaTalleres de C |
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