At subduction zones, continental magmatic arcs are produced by differentiation processes. The Puerto Vallarta Batholith, at the Mexican Pacific margin, is the final product of the subduction of oceanic Farallon plate beneath the North American plate during the Cretaceous. Although this Cordilleran Batholith has been subject to different studies, its petrogenetic evolution remains unclear. To better constrain the magmatic processes that gave origin to the granitic rocks of the Puerto Vallarta Batholith, we combined detailed fieldwork, zircon petrochronology, and conventional thermobarometry coupled with phase equilibrium modeling. We present the crystallization and emplacement evolution, and its relationship to magmatic processes of the Puerto Vallarta Batholith. In the granitic rocks, we observed calc-alkaline and metaluminous signatures, as well as enrichment in light-rare earth elements (LREE) relative to the heavy-rare earth elements (HREE). The early crystallization stages of the Puerto Vallarta Batholith started at ~729–776 °C and ~3.5–5.3 kbar, with the last melt portion crystallized at ~675–685 °C. Fieldwork observations and Zr saturation thermometry reveal mixing of melts during the last crystallization stages. Geochemical signatures of zircons from granitic rocks suggest crystallization after minor plagioclase fractionation with likely assimilation of crustal components. Our results from geochemical whole-rock data further indicate partial melting of a heterogenous source in the mantle wedge and the differentiation of those primary melts as the principal processes that gave origin to the Puerto Vallarta Batholith. We show that the magmatic processes that originated the granitic rocks of this Cordilleran Batholith occurred in the middle crust during the Late Cretaceous. Our results provide new evidence to better constrain the origin of this magmatic system.