Striker Adolfo Bautista, who scored twice, put the Chivas ahead in Saturday's match at the Jalisco stadium with a lob over goalkeeper Jorge Villalpando in the seventh minute.
Bautista restored Guadalajara's lead with a header from Alberto Medina's cross on the stroke of halftime after Puebla's solitary striker, American Hercules Gomez, had equalised in the 22nd minute.
The home side went further ahead two minutes after halftime when midfielder Xavier Baez scored from a cross from the left wing by Omar Bravo.
Uruguayan midfielder Marcelo Palau set up an exciting final half hour of all-out attack when he pulled another back for Puebla.
Guadalajara keeper Luis Michel made good saves from Palau and Guatemalan Carlos Ruiz and at the other end Puebla defender Roberto Juarez cleared a shot from Bravo off the line.
Champions Monterrey beat Queretaro 3-0, while struggling Mexico City giants America host Tigres UANL on Sunday.
America have been without key Paraguay forward Salvador Cabanas for almost a month since he was shot in the head in a Mexico City bar The gunman, whom police have identified, is still on the run.
Cabanas, 29, who still has the bullet lodged in his brain, walked with the support of a frame for the first time on Saturday, 27 days after the shooting, doctors said.
He was taking part in physiotherapy and eating normally, they added.
