Canada impressed in Denver but Mexico's class was telling as an Andres Guardado brace and Roberto Alvarado strike led Martino's men to back-to-back Group A wins.
Alvarado smashed home the opener in the 40th minute before Guardado – a first-half replacement for injured team-mate Erick Gutierrez – made it 2-0 with a stunning long-range effort nine minutes into the second half.
Lucas Cavallini gave Canada some hope with 15 minutes remaining, however, Guardado's second two minutes later sealed a sixth successive victory for Mexico.
Canada – without a win against Mexico since its extra-time victory at the 2000 Gold Cup – frustrated the seven-time champion for much of the opening period.
Canada – which eased past Martinique 4-0 in its first match – was well organised but it almost came unstuck when Jonathan dos Santos blazed a fierce volley over the crossbar.
Mexico did make the breakthrough five minutes prior to half-time after Canada failed to deal with a cross as Raul Jimenez's reflex shot was well saved but the ball fell to the feet of Alvarado and he emphatically converted the rebound.
Canada almost restored parity minutes later via Cavallini, who outmuscled and outran his opponent and forced a save from Guillermo Ochoa.
Relatively quiet in the first half, Bayern Munich sensation Alphonso Davies went agonisingly close to equalising for Canada after ghosting beyond two defenders and seeing his shot flash just wide of the back post.
However, Mexico went up the other end and doubled its lead in the 54th minute when a loose clearance went straight to Guardado, who hit an unstoppable shot past Milan Borjan.
Canada refused to surrender as Jonathan Osorio went close twice and its effort was rewarded after Cavallini bundled home a goal with 15 minutes remaining. However, its hopes were dashed within minutes as Guardado completed his brace.