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| U | CF Pachuca | - | Club León | 2:0 (0:0) | ||
| R | Club León | - | CF Pachuca | 0:1 (0:1) | ||
| U: 17.11.2021 16:30 | R: 20.11.2021 16:00 | Winnaars: CF Pachuca | ||||
| U | Atlas Guadalajara | - | Mazatlán FC | 0:0 (0:0) | ||
| R | Mazatlán FC | - | Atlas Guadalajara | 0:2 (0:0) | ||
| U: 17.11.2021 16:30 | R: 20.11.2021 18:30 | Winnaars: Atlas Guadalajara | ||||
| U | UANL Tigres | - | CF América | 1:1 (0:0) | ||
| R | CF América | - | UANL Tigres | 3:1 (2:0) | ||
| U: 18.11.2021 16:00 | R: 21.11.2021 18:00 | Winnaars: CF América | ||||
| U | Santos Laguna | - | Club Necaxa | 1:0 (0:0) | ||
| R | Club Necaxa | - | Santos Laguna | 3:2 (1:1) | ||
| U: 18.11.2021 17:00 | R: 21.11.2021 16:00 | Winnaars: Santos Laguna | ||||
