CD Marathón 2-7 Portland Timbers *
| 14.04.2021 | Portland Timbers | 5-0 | CD Marathón | |
| 07.04.2021 | CD Marathón | 2-2 | Portland Timbers | |
Atlético Pantoja 1-6 CF Monterrey *
| 16.04.2021 | CF Monterrey | 3-1 | Atlético Pantoja | |
| 09.04.2021 | Atlético Pantoja | 0-3 | CF Monterrey | |
CD Olimpia 2-2 Club América *
| 15.04.2021 | Club América | 0-1 | CD Olimpia | |
| 08.04.2021 | CD Olimpia | 1-2 | Club América | |
Arcahaie FC 0-8 Cruz Azul *
| 14.04.2021 | Cruz Azul | 8-0 | Arcahaie FC | |
| 07.04.2021 | Arcahaie FC | 0-0 | Cruz Azul | |
LD Alajuelense 0-2 Atlanta United *
| 14.04.2021 | Atlanta United | 1-0 | LD Alajuelense | |
| 07.04.2021 | LD Alajuelense | 0-1 | Atlanta United | |
Saprissa 0-5 Philadelphia Union *
| 15.04.2021 | Philadelphia Union | 4-0 | Saprissa | |
| 08.04.2021 | Saprissa | 0-1 | Philadelphia Union | |
Real Estelí 0-5 Columbus Crew *
| 16.04.2021 | Columbus Crew | 1-0 | Real Estelí | |
| 09.04.2021 | Real Estelí | 0-4 | Columbus Crew | |
Club León 2-3 Toronto FC *
| 15.04.2021 | Toronto FC | 2-1 | Club León | |
| 08.04.2021 | Club León | 1-1 | Toronto FC | |