Santos, runners-up in the Apertura in December, won 3-2 on aggregate after a 1-1 draw in Thursday's first leg at Monterrey.
Midfielder Daniel Luduena put Santos ahead after five minutes and striker Oribe Peralta scored the decisive second in the 64th, with Jesus de Nigris pulling one back 12 minutes from time in Sunday's match at the Corona in the city of Torreon.
Peralta has been the key for Santos, scoring the two late goals that gave them victory over Apertura winners Tigres UANL in the second leg of their semi-final last weekend and also finding the net in both legs of the final.
"I'm now at the most important stage in my career (but) I have a lot of dreams still to fulfil," the 28-year-old said.
"I still have a contract here for several years and I hope to stay on," added the former Monterrey player when asked about interest from other clubs.
It was Monterrey coach Victor Vucetich's first defeat in 13 finals. He steered his team to the CONCACAF Champions League title this season.
Santos became the first team since 2007 to win the championship, decided in an eight-team knockout phase, having finished top of the 17-match league stage.