1st(1st leg) CF Pachuca - Club León 2:0 (0:0)
2nd (2nd leg) Club León - CF Pachuca 0:1 (0:1)
1st(1st leg): 17/11/2021 15:30 2nd (2nd leg): 20/11/2021 15:00 Winner: CF Pachuca
1st(1st leg) Atlas Guadalajara - Mazatlán FC 0:0 (0:0)
2nd (2nd leg) Mazatlán FC - Atlas Guadalajara 0:2 (0:0)
1st(1st leg): 17/11/2021 15:30 2nd (2nd leg): 20/11/2021 17:30 Winner: Atlas Guadalajara
1st(1st leg) UANL Tigres - CF América 1:1 (0:0)
2nd (2nd leg) CF América - UANL Tigres 3:1 (2:0)
1st(1st leg): 18/11/2021 15:00 2nd (2nd leg): 21/11/2021 17:00 Winner: CF América
1st(1st leg) Santos Laguna - Club Necaxa 1:0 (0:0)
2nd (2nd leg) Club Necaxa - Santos Laguna 3:2 (1:1)
1st(1st leg): 18/11/2021 16:00 2nd (2nd leg): 21/11/2021 15:00 Winner: Santos Laguna