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| 1st(1st leg) | Deportivo Toluca | - | Cruz Azul | 2:1 (1:1) | ||
| 2nd (2nd leg) | Cruz Azul | - | Deportivo Toluca | 3:1 (1:1) | ||
| 1st(1st leg): 13/05/2021 01:00 | 2nd (2nd leg): 16/05/2021 02:05 | Winner: Cruz Azul | ||||
| 1st(1st leg) | Atlas Guadalajara | - | Puebla FC | 1:0 (0:0) | ||
| 2nd (2nd leg) | Puebla FC | - | Atlas Guadalajara | 1:0 (0:0) | ||
| 1st(1st leg): 13/05/2021 03:05 | 2nd (2nd leg): 16/05/2021 00:00 | |||||
| 1st(1st leg) | CF Pachuca | - | CF América | 3:1 (1:1) | ||
| 2nd (2nd leg) | CF América | - | CF Pachuca | 4:2 (2:1) | ||
| 1st(1st leg): 14/05/2021 01:00 | 2nd (2nd leg): 17/05/2021 02:05 | Winner: CF Pachuca | ||||
| 1st(1st leg) | Santos Laguna | - | CF Monterrey | 2:1 (0:1) | ||
| 2nd (2nd leg) | CF Monterrey | - | Santos Laguna | 1:1 (1:0) | ||
| 1st(1st leg): 14/05/2021 03:05 | 2nd (2nd leg): 17/05/2021 00:00 | Winner: Santos Laguna | ||||
