A Atlanta United FC - Philadelphia Union 0:3 (0:0)
R Philadelphia Union - Atlanta United FC 1:1 (0:1)
A: 28.04.2021 02:00 R: 05.05.2021 02:00 Vincitore: Philadelphia Union
A Toronto FC - Cruz Azul 1:3 (1:2)
R Cruz Azul - Toronto FC 1:0 (1:0)
A: 28.04.2021 04:00 R: 05.05.2021 04:15 Vincitore: Cruz Azul
A Columbus Crew - CF Monterrey 2:2 (0:1)
R CF Monterrey - Columbus Crew 3:0 (2:0)
A: 29.04.2021 02:30 R: 06.05.2021 02:00 Vincitore: CF Monterrey
A Portland Timbers - CF América 1:1 (0:1)
R CF América - Portland Timbers 3:1 (1:0)
A: 29.04.2021 04:30 R: 06.05.2021 04:15 Vincitore: CF América