| 16 Mar 21 | Qualifier     | CSD MacaráCSD Macará | 2 - 2 | EmelecEmelec |
| 16 Mar 21 | Qualifier | 12 de Octubre12 de Octubre | 0 - 0 | Club NacionalClub Nacional |
| 17 Mar 21 | Qualifier | Deportes TolimaDeportes Toli | 3 - 0 | Deportivo CaliDeportivo Cal |
| 17 Mar 21 | Qualifier | Deportes AntofagastaDeportes Anto | 0 - 1 | HuachipatoHuachipato |
| 17 Mar 21 | Qualifier | Club Deportivo GuabiráClub Deportiv | 4 - 1 | Nacional PotosíNacional Poto |
| 18 Mar 21 | Qualifier | Universidad Técnica de CaUniversidad T | 0 - 1 | Sport HuancayoSport Huancay |
| 18 Mar 21 | Qualifier | Aragua F.C.Aragua F.C. | 0 - 1 | Mineros de GuayanaMineros de Gu |
| 18 Mar 21 | Qualifier | WilstermannWilstermann | 2 - 1 | Atlético PalmaflorAtlético Palm |
| 18 Mar 21 | Qualifier | SD AucasSD Aucas | 1 - 1 | Guayaquil City FCGuayaquil Cit |
| 18 Mar 21 | Qualifier | Guaireña FCGuaireña FC | 1 - 2 | Club River Plate AsunciónClub River Pl |
| 18 Mar 21 | Qualifier | Metropolitanos F.C.Metropolitano | 2 - 0 | Puerto Cabello F.C.Puerto Cabell |
| 19 Mar 21 | Qualifier | La EquidadLa Equidad | 1 - 2 | Deportivo PastoDeportivo Pas |
| 19 Mar 21 | Qualifier | Carlos A MannucciCarlos A Mann | 1 - 2 | FBC MelgarFBC Melgar |
| 19 Mar 21 | Qualifier | CobresalCobresal | 0 - 0 | PalestinoPalestino |
| 06 Apr 21 | Qualifier | Club NacionalClub Nacional | 0 - 0 | 12 de Octubre12 de Octubre |
| 06 Apr 21 | Qualifier | EmelecEmelec | 2 - 0 | CSD MacaráCSD Macará |
| 07 Apr 21 | Qualifier | Deportivo CaliDeportivo Cal | 0 - 0 | Deportes TolimaDeportes Toli |
| 07 Apr 21 | Qualifier | Cerro Largo FCCerro Largo F | 2 - 2 | PeñarolPeñarol |
| 07 Apr 21 | Qualifier | HuachipatoHuachipato | 3 - 0 | Deportes AntofagastaDeportes Anto |
| 07 Apr 21 | Qualifier | Mineros de GuayanaMineros de Gu | 1 - 2 | Aragua F.C.Aragua F.C. |
| 07 Apr 21 | Qualifier | Nacional PotosíNacional Poto | 1 - 2 | Club Deportivo GuabiráClub Deportiv |
| 07 Apr 21 | Qualifier | Montevideo City TorqueMontevideo Ci | 0 - 0 | FenixFenix |
| 08 Apr 21 | Qualifier | Atlético PalmaflorAtlético Palm | 1 - 2 | WilstermannWilstermann |
| 08 Apr 21 | Qualifier | Sport HuancayoSport Huancay | 3 - 0 | Universidad Técnica de CaUniversidad T |
| 08 Apr 21 | Qualifier | Guayaquil City FCGuayaquil Cit | 0 - 3 | SD AucasSD Aucas |
| 08 Apr 21 | Qualifier | Puerto Cabello F.C.Puerto Cabell | 0 - 1 | Metropolitanos F.C.Metropolitano |
| 08 Apr 21 | Qualifier | Club River Plate AsunciónClub River Pl | 4 - 2 | Guaireña FCGuaireña FC |
| 09 Apr 21 | Qualifier | FBC MelgarFBC Melgar | 3 - 2 | Carlos A MannucciCarlos A Mann |
| 09 Apr 21 | Qualifier | Deportivo PastoDeportivo Pas | 0 - 2 | La EquidadLa Equidad |
| 09 Apr 21 | Qualifier | PalestinoPalestino | 2 - 1 | CobresalCobresal |
| 14 Apr 21 | Qualifier | PeñarolPeñarol | 4 - 1 | Cerro Largo FCCerro Largo F |
| 14 Apr 21 | Qualifier | FenixFenix | 0 - 2 | Montevideo City TorqueMontevideo Ci |
| |
| 20 Apr 21 | r01 | Metropolitanos F.C.Metropolitano | 2 - 3 | FBC MelgarFBC Melgar |
| 20 Apr 21 | r01 | Atletico GOAtletico GO | 0 - 0 | Newells Old BoysNewells Old B |
| 21 Apr 21 | r01 | 12 de Octubre12 de Octubre | 1 - 0 | Rosario CentralRosario Centr |
| 21 Apr 21 | r01 | SD AucasSD Aucas | 0 - 1 | Atletico PRAtletico PR |
| 21 Apr 21 | r01 | San LorenzoSan Lorenzo | 0 - 1 | HuachipatoHuachipato |
| 21 Apr 21 | r01 | CearaCeara | 3 - 1 | WilstermannWilstermann |
| 22 Apr 21 | r01 | Montevideo City TorqueMontevideo Ci | 1 - 1 | BahiaBahia |
| 22 Apr 21 | r01 | Club Deportivo GuabiráClub Deportiv | 1 - 3 | IndependienteIndependiente |
| 22 Apr 21 | r01 | Talleres de CordobaTalleres de C | 1 - 2 | EmelecEmelec |
| 22 Apr 21 | r01 | BolivarBolivar | 2 - 1 | Arsenal SarandiArsenal Saran |
| 22 Apr 21 | r01 | BragantinoBragantino | 2 - 1 | Deportes TolimaDeportes Toli |
| 22 Apr 21 | r01 | GremioGremio | 2 - 1 | La EquidadLa Equidad |
| 22 Apr 21 | r01 | Aragua F.C.Aragua F.C. | 0 - 1 | LanusLanus |
| 23 Apr 21 | r01 | PeñarolPeñarol | 5 - 1 | Sport HuancayoSport Huancay |
| 23 Apr 21 | r01 | Club River Plate AsunciónClub River Pl | 0 - 0 | CorinthiansCorinthians |
| 23 Apr 21 | r01 | Club LibertadClub Libertad | 2 - 0 | PalestinoPalestino |
| |
| 27 Apr 21 | r02 | BahiaBahia | 5 - 0 | Club Deportivo GuabiráClub Deportiv |
| 28 Apr 21 | r02 | HuachipatoHuachipato | 0 - 0 | 12 de Octubre12 de Octubre |
| 28 Apr 21 | r02 | Arsenal SarandiArsenal Saran | 0 - 0 | CearaCeara |
| 28 Apr 21 | r02 | IndependienteIndependiente | 3 - 1 | Montevideo City TorqueMontevideo Ci |
| 28 Apr 21 | r02 | Atletico PRAtletico PR | 1 - 0 | Metropolitanos F.C.Metropolitano |
| 29 Apr 21 | r02 | Rosario CentralRosario Centr | 2 - 0 | San LorenzoSan Lorenzo |
| 29 Apr 21 | r02 | FBC MelgarFBC Melgar | 2 - 0 | SD AucasSD Aucas |
| 29 Apr 21 | r02 | Deportes TolimaDeportes Toli | 1 - 1 | Talleres de CordobaTalleres de C |
| 29 Apr 21 | r02 | EmelecEmelec | 3 - 0 | BragantinoBragantino |
| 29 Apr 21 | r02 | WilstermannWilstermann | 0 - 0 | BolivarBolivar |
| 29 Apr 21 | r02 | Sport HuancayoSport Huancay | 1 - 2 | Club River Plate AsunciónClub River Pl |
| 29 Apr 21 | r02 | CorinthiansCorinthians | 0 - 2 | PeñarolPeñarol |
| 30 Apr 21 | r02 | PalestinoPalestino | 0 - 1 | Atletico GOAtletico GO |
| 30 Apr 21 | r02 | Newells Old BoysNewells Old B | 1 - 3 | Club LibertadClub Libertad |
| 30 Apr 21 | r02 | La EquidadLa Equidad | 2 - 1 | Aragua F.C.Aragua F.C. |
| 30 Apr 21 | r02 | LanusLanus | 1 - 2 | GremioGremio |
| |
| 04 May 21 | r03 | BahiaBahia | 2 - 2 | IndependienteIndependiente |
| 04 May 21 | r03 | Metropolitanos F.C.Metropolitano | 3 - 2 | SD AucasSD Aucas |
| 05 May 21 | r03 | FBC MelgarFBC Melgar | 1 - 0 | Atletico PRAtletico PR |
| 05 May 21 | r03 | PalestinoPalestino | 0 - 1 | Newells Old BoysNewells Old B |
| 05 May 21 | r03 | HuachipatoHuachipato | 1 - 1 | Rosario CentralRosario Centr |
| 05 May 21 | r03 | Montevideo City TorqueMontevideo Ci | 4 - 0 | Club Deportivo GuabiráClub Deportiv |
| 05 May 21 | r03 | BolivarBolivar | 0 - 0 | CearaCeara |
| 06 May 21 | r03 | BragantinoBragantino | 0 - 1 | Talleres de CordobaTalleres de C |
| 06 May 21 | r03 | Arsenal SarandiArsenal Saran | 3 - 0 | WilstermannWilstermann |
| 06 May 21 | r03 | Club LibertadClub Libertad | 1 - 2 | Atletico GOAtletico GO |
| 06 May 21 | r03 | GremioGremio | 8 - 0 | Aragua F.C.Aragua F.C. |
| 07 May 21 | r03 | San LorenzoSan Lorenzo | 1 - 1 | 12 de Octubre12 de Octubre |
| 07 May 21 | r03 | Sport HuancayoSport Huancay | 0 - 3 | CorinthiansCorinthians |
| 07 May 21 | r03 | PeñarolPeñarol | 3 - 0 | Club River Plate AsunciónClub River Pl |
| 07 May 21 | r03 | La EquidadLa Equidad | 0 - 1 | LanusLanus |
| 08 May 21 | r03 | Deportes TolimaDeportes Toli | 1 - 1 | EmelecEmelec |
| |
| 11 May 21 | r04 | Metropolitanos F.C.Metropolitano | 0 - 1 | Atletico PRAtletico PR |
| 11 May 21 | r04 | BragantinoBragantino | 2 - 0 | EmelecEmelec |
| 12 May 21 | r04 | Montevideo City TorqueMontevideo Ci | 1 - 1 | IndependienteIndependiente |
| 12 May 21 | r04 | Talleres de CordobaTalleres de C | 0 - 0 | Deportes TolimaDeportes Toli |
| 12 May 21 | r04 | 12 de Octubre12 de Octubre | 1 - 2 | HuachipatoHuachipato |
| 12 May 21 | r04 | CearaCeara | 0 - 0 | Arsenal SarandiArsenal Saran |
| 13 May 21 | r04 | San LorenzoSan Lorenzo | 1 - 2 | Rosario CentralRosario Centr |
| 13 May 21 | r04 | BolivarBolivar | 2 - 2 | WilstermannWilstermann |
| 13 May 21 | r04 | Atletico GOAtletico GO | 0 - 0 | PalestinoPalestino |
| 13 May 21 | r04 | Club Deportivo GuabiráClub Deportiv | 0 - 1 | BahiaBahia |
| 13 May 21 | r04 | Aragua F.C.Aragua F.C. | 1 - 2 | La EquidadLa Equidad |
| 13 May 21 | r04 | GremioGremio | 3 - 1 | LanusLanus |
| 14 May 21 | r04 | SD AucasSD Aucas | 2 - 1 | FBC MelgarFBC Melgar |
| 14 May 21 | r04 | Club River Plate AsunciónClub River Pl | 2 - 1 | Sport HuancayoSport Huancay |
| 14 May 21 | r04 | PeñarolPeñarol | 4 - 0 | CorinthiansCorinthians |
| 14 May 21 | r04 | Club LibertadClub Libertad | 1 - 0 | Newells Old BoysNewells Old B |
| |
| 18 May 21 | r05 | IndependienteIndependiente | 1 - 0 | BahiaBahia |
| 18 May 21 | r05 | Club River Plate AsunciónClub River Pl | 2 - 1 | PeñarolPeñarol |
| 19 May 21 | r05 | Talleres de CordobaTalleres de C | 0 - 1 | BragantinoBragantino |
| 19 May 21 | r05 | WilstermannWilstermann | 1 - 2 | Arsenal SarandiArsenal Saran |
| 19 May 21 | r05 | Atletico GOAtletico GO | 0 - 0 | Club LibertadClub Libertad |
| 19 May 21 | r05 | EmelecEmelec | 2 - 0 | Deportes TolimaDeportes Toli |
| 20 May 21 | r05 | Rosario CentralRosario Centr | 5 - 0 | HuachipatoHuachipato |
| 20 May 21 | r05 | Atletico PRAtletico PR | 1 - 0 | FBC MelgarFBC Melgar |
| 20 May 21 | r05 | SD AucasSD Aucas | 3 - 0 | Metropolitanos F.C.Metropolitano |
| 20 May 21 | r05 | 12 de Octubre12 de Octubre | 0 - 2 | San LorenzoSan Lorenzo |
| 20 May 21 | r05 | CearaCeara | 2 - 0 | BolivarBolivar |
| 20 May 21 | r05 | Newells Old BoysNewells Old B | 3 - 1 | PalestinoPalestino |
| 21 May 21 | r05 | Club Deportivo GuabiráClub Deportiv | 0 - 4 | Montevideo City TorqueMontevideo Ci |
| 21 May 21 | r05 | CorinthiansCorinthians | 5 - 0 | Sport HuancayoSport Huancay |
| 21 May 21 | r05 | LanusLanus | 4 - 1 | La EquidadLa Equidad |
| 21 May 21 | r05 | Aragua F.C.Aragua F.C. | 2 - 6 | GremioGremio |
| |
| 25 May 21 | r06 | PalestinoPalestino | 1 - 2 | Club LibertadClub Libertad |
| 25 May 21 | r06 | Newells Old BoysNewells Old B | 1 - 1 | Atletico GOAtletico GO |
| 26 May 21 | r06 | EmelecEmelec | 1 - 4 | Talleres de CordobaTalleres de C |
| 26 May 21 | r06 | Deportes TolimaDeportes Toli | 1 - 2 | BragantinoBragantino |
| 26 May 21 | r06 | IndependienteIndependiente | 1 - 0 | Club Deportivo GuabiráClub Deportiv |
| 26 May 21 | r06 | BahiaBahia | 2 - 4 | Montevideo City TorqueMontevideo Ci |
| 27 May 21 | r06 | Rosario CentralRosario Centr | 0 - 0 | 12 de Octubre12 de Octubre |
| 27 May 21 | r06 | HuachipatoHuachipato | 0 - 3 | San LorenzoSan Lorenzo |
| 27 May 21 | r06 | CorinthiansCorinthians | 4 - 0 | Club River Plate AsunciónClub River Pl |
| 27 May 21 | r06 | Sport HuancayoSport Huancay | 0 - 0 | PeñarolPeñarol |
| 27 May 21 | r06 | WilstermannWilstermann | 1 - 0 | CearaCeara |
| 27 May 21 | r06 | Arsenal SarandiArsenal Saran | 3 - 1 | BolivarBolivar |
| 28 May 21 | r06 | Atletico PRAtletico PR | 4 - 0 | SD AucasSD Aucas |
| 28 May 21 | r06 | FBC MelgarFBC Melgar | 0 - 0 | Metropolitanos F.C.Metropolitano |
| 28 May 21 | r06 | LanusLanus | 0 - 0 | Aragua F.C.Aragua F.C. |
| 28 May 21 | r06 | La EquidadLa Equidad | 0 - 0 | GremioGremio |
| |
| 13 Jul 21 | r16 | LDU QuitoLDU Quito | 0 - 1 | GremioGremio |
| 14 Jul 21 | r16 | América de CaliAmérica de Ca | 0 - 1 | Atletico PRAtletico PR |
| 14 Jul 21 | r16 | Sporting CristalSporting Cris | 2 - 1 | Arsenal SarandiArsenal Saran |
| 15 Jul 21 | r16 | Atlético JuniorAtlético Juni | 3 - 4 | Club LibertadClub Libertad |
| 15 Jul 21 | r16 | Independiente del ValleIndependiente | 0 - 2 | BragantinoBragantino |
| 15 Jul 21 | r16 | Santos FCSantos FC | 1 - 0 | IndependienteIndependiente |
| 16 Jul 21 | r16 | Nacional MontevideoNacional Mont | 1 - 2 | PeñarolPeñarol |
| 16 Jul 21 | r16 | Deportivo Táchira F.C.Deportivo Tác | 2 - 2 | Rosario CentralRosario Centr |
| 20 Jul 21 | r16 | GremioGremio | 1 - 2 | LDU QuitoLDU Quito |
| 21 Jul 21 | r16 | Atletico PRAtletico PR | 4 - 1 | América de CaliAmérica de Ca |
| 21 Jul 21 | r16 | Arsenal SarandiArsenal Saran | 1 - 1 | Sporting CristalSporting Cris |
| 22 Jul 21 | r16 | BragantinoBragantino | 1 - 1 | Independiente del ValleIndependiente |
| 22 Jul 21 | r16 | Club LibertadClub Libertad | 0 - 1 | Atlético JuniorAtlético Juni |
| 22 Jul 21 | r16 | IndependienteIndependiente | 1 - 1 | Santos FCSantos FC |
| 23 Jul 21 | r16 | PeñarolPeñarol | 0 - 1 | Nacional MontevideoNacional Mont |
| 23 Jul 21 | r16 | Rosario CentralRosario Centr | 1 - 0 | Deportivo Táchira F.C.Deportivo Tác |
| |
| 10 Aug 21 | QF | Rosario CentralRosario Centr | 3 - 4 | BragantinoBragantino |
| 11 Aug 21 | QF | Sporting CristalSporting Cris | 1 - 3 | PeñarolPeñarol |
| 12 Aug 21 | QF | LDU QuitoLDU Quito | 1 - 0 | Atletico PRAtletico PR |
| 13 Aug 21 | QF | Santos FCSantos FC | 2 - 1 | Club LibertadClub Libertad |
| 17 Aug 21 | QF | BragantinoBragantino | 1 - 0 | Rosario CentralRosario Centr |
| 18 Aug 21 | QF | PeñarolPeñarol | 1 - 0 | Sporting CristalSporting Cris |
| 19 Aug 21 | QF | Atletico PRAtletico PR | 4 - 2 | LDU QuitoLDU Quito |
| 20 Aug 21 | QF | Club LibertadClub Libertad | 1 - 0 | Santos FCSantos FC |
| |
| 22 Sep 21 | SF | BragantinoBragantino | 2 - 0 | Club LibertadClub Libertad |
| 24 Sep 21 | SF | PeñarolPeñarol | 1 - 2 | Atletico PRAtletico PR |
| 29 Sep 21 | SF | Club LibertadClub Libertad | 1 - 3 | BragantinoBragantino |
| 01 Oct 21 | SF | Atletico PRAtletico PR | 2 - 0 | PeñarolPeñarol |
| |
| 20 Nov 21 | Final | Atletico PRAtletico PR | 1 - 0 | BragantinoBragantino |
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