In a pulsating first half of football at the Estadio Leon, both teams missed several chances but the hosts still managed to build a match-winning lead, scoring four times.
While Santos Laguna struck twice after the break, Leon held on for victory, their second in a row in Liga MX.
Leon moved up to seventh spot in the Mexican league table with 11 points, just ahead of Chiapas on goal difference, while Santos Laguna (10 points) dropped out of the Liga MX finals positions to sit ninth.
It took just eight minutes for Leon to hit the front on Saturday with Elias Hernandez cutting inside onto his right foot and curling the ball inside the far post.
Matias Britos scored the home side's second goal in the 19th minute, getting to a long pass first and, despite being upended by a Santos defender, half-volleying the ball into the net.
The game continued in an end-to-end fashion and Carlos Pena struck next for Leon, bursting through the middle of the visiting defence in the 34th minute, evading three opponents and then shooting across Santos goalkeeper Oswaldo Sanchez to score.
Leon completed a brilliant first half when Miguel Sabah side-footed home in the 45th minute after a right-wing cross somehow evaded two Santos defenders.
After a terrible first-half performance, Santos were handed a glimmer of hope two minutes after the break when substitute Mauro Cejas thrashed the ball home from the edge of the area.
But the visitors were unable to score at a regular enough rate to have a chance of getting back into the contest with Oribe Peralta scoring Santos' second goal with 20 minutes remaining.
Santos received another blow in the 90th minute when Jonathan Lacerda was shown his second yellow card and sent off.
Liga MX leaders Cruz Azul continued their unbeaten start to the Clausura season with a 3-1 win at Queretaro on Friday.
Cruz Azul lead the league with 22 points, while Toluca (19 points) are second after their 1-0 win over Guadalajara on Sunday.
Third-placed Pumas UNAM rose to 14 points with a 3-1 win at America, while Pachuca (13 points) moved up to fourth after dispatching with Morelia 3-0.
America's third loss in a row saw them drop to fifth with 12 points, just ahead of Guadalajara on goal difference.
In other Liga MX results, Chiapas won 3-0 at Tijuana, Tigres UANL defeated Veracruz 1-0, Monterrey edged out Atlas by the same scoreline and Atlante were held to a scoreless draw by Puebla.
