Paraguayan Pablo Aguilar scored San Luis's winner in the 77th minute, heading home a corner from Colombian Tressor Moreno.
On Saturday, Cruz Azul came from two goals down to draw 4-4 at Puebla.
Midfielder Jaime Lozano scored both second-half goals for Cruz Azul to leave them needing only draw in their home leg next weekend to go through thanks to having finished the qualifying group stage better placed than Puebla.
Surprisingly none of Cruz Azul's four goals came from Argentine striker Emanuel Villa, the championship's top scorer with 17.
Uruguayan trio Nicolas Olivera, Alejandro Acosta and Nicolas Vigneri and Mexico World Cup striker Jared Borgetti gave Puebla a 4-2 halftime lead with replies from Melvin Brown and Gerardo Torrado.
Lozano converted a 51st-minute penalty then brilliantly headed the 82nd-minute equaliser from a free kick taken Rogelio Chavez.
Santos Laguna won the first leg of their quarter-final against Morelia 2-1 with two goals by Carlos Ochoa, but they had Argentine-born striker Matias Vuoso sent off for dissent.
Monterrey beat America 1-0 with a goal by Aldo De Nigris, brother of Larissa forward Antonio, who died of a heart attack in Greece on Monday.
"I'm going to dedicate this match and my life to my brother. I'm happy because I know he's watching me, that he was here and he helped me," an emotional De Nigris told Televisa.
Alexia Putellas: "We’re already the only club to have won the men’s and women’s Champions League, so the only thing even more historic to do than that would be to win it in the same season"
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