1st(1st leg) Atlanta United FC - Philadelphia Union 0:3 (0:0)
2nd (2nd leg) Philadelphia Union - Atlanta United FC 1:1 (0:1)
1st(1st leg): 28/04/2021 01:00 2nd (2nd leg): 05/05/2021 01:00 Winner: Philadelphia Union
1st(1st leg) Toronto FC - Cruz Azul 1:3 (1:2)
2nd (2nd leg) Cruz Azul - Toronto FC 1:0 (1:0)
1st(1st leg): 28/04/2021 03:00 2nd (2nd leg): 05/05/2021 03:15 Winner: Cruz Azul
1st(1st leg) Columbus Crew - CF Monterrey 2:2 (0:1)
2nd (2nd leg) CF Monterrey - Columbus Crew 3:0 (2:0)
1st(1st leg): 29/04/2021 01:30 2nd (2nd leg): 06/05/2021 01:00 Winner: CF Monterrey
1st(1st leg) Portland Timbers - CF América 1:1 (0:1)
2nd (2nd leg) CF América - Portland Timbers 3:1 (1:0)
1st(1st leg): 29/04/2021 03:30 2nd (2nd leg): 06/05/2021 03:15 Winner: CF América