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| 1st(1st leg) | Cruz Azul | - | Atlas Guadalajara | 0:4 (0:3) | ||
| 2nd (2nd leg) | Atlas Guadalajara | - | Cruz Azul | 0:3 (0:2) | ||
| 1st(1st leg): 05/05/2021 15:00 | 2nd (2nd leg): 08/05/2021 15:00 | Winner: Atlas Guadalajara | ||||
| 1st(1st leg) | Santos Laguna | - | Pumas UNAM | 0:0 (0:0) | ||
| 2nd (2nd leg) | Pumas UNAM | - | Santos Laguna | 1:1 (0:0) | ||
| 1st(1st leg): 05/05/2021 15:00 | 2nd (2nd leg): 08/05/2021 17:00 | Winner: Santos Laguna | ||||
| 1st(1st leg) | Deportivo Toluca | - | CF Pachuca | 2:2 (1:1) | ||
| 2nd (2nd leg) | CF Pachuca | - | Deportivo Toluca | 2:0 (2:0) | ||
| 1st(1st leg): 05/05/2021 17:30 | 2nd (2nd leg): 08/05/2021 15:30 | Winner: CF Pachuca | ||||
| 1st(1st leg) | Deportivo Guadalajara | - | Club León | 0:0 (0:0) | ||
| 2nd (2nd leg) | Club León | - | Deportivo Guadalajara | 1:1 (0:1) | ||
| 1st(1st leg): 06/05/2021 16:00 | 2nd (2nd leg): 09/05/2021 17:30 | Winner: Deportivo Guadalajara | ||||
