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| H (Match allé) | Deportivo Toluca | - | Cruz Azul | 2:1 (1:1) | ||
| R (match retour) | Cruz Azul | - | Deportivo Toluca | 3:1 (1:1) | ||
| H (Match allé): 13.05.2021 02:00 | R (match retour): 16.05.2021 03:05 | vainqueur: Cruz Azul | ||||
| H (Match allé) | Atlas Guadalajara | - | Puebla FC | 1:0 (0:0) | ||
| R (match retour) | Puebla FC | - | Atlas Guadalajara | 1:0 (0:0) | ||
| H (Match allé): 13.05.2021 04:05 | R (match retour): 16.05.2021 01:00 | |||||
| H (Match allé) | CF Pachuca | - | CF América | 3:1 (1:1) | ||
| R (match retour) | CF América | - | CF Pachuca | 4:2 (2:1) | ||
| H (Match allé): 14.05.2021 02:00 | R (match retour): 17.05.2021 03:05 | vainqueur: CF Pachuca | ||||
| H (Match allé) | Santos Laguna | - | CF Monterrey | 2:1 (0:1) | ||
| R (match retour) | CF Monterrey | - | Santos Laguna | 1:1 (1:0) | ||
| H (Match allé): 14.05.2021 04:05 | R (match retour): 17.05.2021 01:00 | vainqueur: Santos Laguna | ||||
