Ecuadorean midfielder Michael Arroyo scored both San Luis goals before Brazilian-born former Mexico midfielder Zinha pulled one back.
San Luis lead Group Two with 25 points, one more than America, who crushed Estudiantes UAG 4-1 at the Azteca in the capital with two goals from striker Daniel Marquez.
Toluca are third three points behind America, while CONCACAF Champions League winners Pachuca, who will play in the Club World Cup in Abu Dhabi in December, are fourth with 19 points and in danger of not reaching the play-offs.
The two teams that finish top of the three groups plus the next two best-placed teams overall at the end of the 17-match round-robin phase qualify for the knockout rounds. There are two matches to go.
Guadalajara, who only three months ago reached South America's Libertadores Cup final, virtually lost all chance of a place in the last eight with a 1-1 draw away to Santos Laguna on Saturday.
The Chivas are fourth in Group One with 18 points, 14 adrift of leaders Monterrey, who won 2-0 away to Morelia to secure their place in the last eight, and eight behind Santos.
Ecuadorean striker Cristian Benitez, who opened the scoring for Santos three minutes from time, is the championship's leading marksman with 13 goals.
Omar Arellano earned a point for the visiting Chivas when he equalised two minutes later.
Group Three leaders Cruz, whose 35 points put them top of the overall standings and who had already clinched a place in the play-offs, beat Puebla 1-0 at home with a goal by Argentine midfielder Christian Gimenez.
Jaguares of Chiapas are second in the group with 21 points after a 0-0 draw with Tigres UANL.
