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| H (Match allé) | Atlanta United FC | - | Philadelphia Union | 0:3 (0:0) | ||
| R (match retour) | Philadelphia Union | - | Atlanta United FC | 1:1 (0:1) | ||
| H (Match allé): 28.04.2021 02:00 | R (match retour): 05.05.2021 02:00 | vainqueur: Philadelphia Union | ||||
| H (Match allé) | Toronto FC | - | Cruz Azul | 1:3 (1:2) | ||
| R (match retour) | Cruz Azul | - | Toronto FC | 1:0 (1:0) | ||
| H (Match allé): 28.04.2021 04:00 | R (match retour): 05.05.2021 04:15 | vainqueur: Cruz Azul | ||||
| H (Match allé) | Columbus Crew | - | CF Monterrey | 2:2 (0:1) | ||
| R (match retour) | CF Monterrey | - | Columbus Crew | 3:0 (2:0) | ||
| H (Match allé): 29.04.2021 02:30 | R (match retour): 06.05.2021 02:00 | vainqueur: CF Monterrey | ||||
| H (Match allé) | Portland Timbers | - | CF América | 1:1 (0:1) | ||
| R (match retour) | CF América | - | Portland Timbers | 3:1 (1:0) | ||
| H (Match allé): 29.04.2021 04:30 | R (match retour): 06.05.2021 04:15 | vainqueur: CF América | ||||
