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| 1st(1st leg) | Atlas Guadalajara | - | CF América | 3:1 (2:0) | ||
| 2nd (2nd leg) | CF América | - | Atlas Guadalajara | 0:2 (0:0) | ||
| 1st(1st leg): 05/05/2021 15:00 | 2nd (2nd leg): 08/05/2021 17:00 | Winner: Atlas Guadalajara | ||||
| 1st(1st leg) | Club León | - | CF Monterrey | 0:1 (0:1) | ||
| 2nd (2nd leg) | CF Monterrey | - | Club León | 3:2 (3:1) | ||
| 1st(1st leg): 05/05/2021 16:00 | 2nd (2nd leg): 08/05/2021 15:00 | Winner: CF Monterrey | ||||
| 1st(1st leg) | Deportivo Toluca | - | Club Tijuana | 1:0 (1:0) | ||
| 2nd (2nd leg) | Club Tijuana | - | Deportivo Toluca | 2:2 (1:0) | ||
| 1st(1st leg): 06/05/2021 15:00 | 2nd (2nd leg): 10/05/2021 05:00 | Winner: Deportivo Toluca | ||||
| 1st(1st leg) | FC Juárez | - | CF Pachuca | 1:1 (1:0) | ||
| 2nd (2nd leg) | CF Pachuca | - | FC Juárez | 0:0 (0:0) | ||
| 1st(1st leg): 06/05/2021 17:00 | 2nd (2nd leg): 09/05/2021 18:00 | Winner: CF Pachuca | ||||
