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| H (Match allé) | Cafetaleros de Chiapas | - | Alacranes de Durango | 0:0 (0:0) | ||
| R (match retour) | Alacranes de Durango | - | Cafetaleros de Chiapas | 0:0 (0:0) | ||
| H (Match allé): 17.04.2021 23:00 | R (match retour): 24.04.2021 03:30 | |||||
| H (Match allé) | Colima FC | - | Inter Playa | 2:2 (1:1) | ||
| R (match retour) | Inter Playa | - | Colima FC | 1:1 (0:1) | ||
| H (Match allé): 18.04.2021 00:00 | R (match retour): 23.04.2021 23:00 | vainqueur: Inter Playa | ||||
| H (Match allé) | Gavilanes de Matamoros | - | Cruz Azul Hidalgo | 0:0 (0:0) | ||
| R (match retour) | Cruz Azul Hidalgo | - | Gavilanes de Matamoros | 1:0 (0:0) | ||
| H (Match allé): 18.04.2021 02:00 | R (match retour): 24.04.2021 23:00 | vainqueur: Cruz Azul Hidalgo | ||||
| H (Match allé) | Reboceros de La Piedad | - | Club Irapuato | 1:1 (0:1) | ||
| R (match retour) | Club Irapuato | - | Reboceros de La Piedad | 4:1 (1:1) | ||
| H (Match allé): 18.04.2021 23:00 | R (match retour): 25.04.2021 02:00 | vainqueur: Club Irapuato | ||||
