This study focuses on two issues that are still a matter of debate in subduction zones, particularly in western México: (1) the close association within the same volcanic complex of typical amphibole-free andesites to rhyolites and amphibole-bearing andesites to rhyolites, characteristic of the hydrated front of the Mexican arc; and (2) the occurrence of bimodal magmatism without evidence for interaction between mafic and intermediate to silicic magmas, which are in addition characterized by different petrogenetic affinities. Our case study is the San Pedro–Cerro Grande volcanic complex, a Quaternary silicic to intermediate dome complex located in western Mexico. Volcanic activity has been divided into two periods. In the middle Pleistocene, andesitic to dacitic magmas were emplaced along WNW-trending faults in the southern portion of the complex. The Las Cuevas pyroclastic sequence (older than ca. 500 ka) was emplaced during this episode, most likely from a local source. This first period of activity ended before ca. 280 ka with the emplacement of the Cuastecomate Plinian deposit, which is related to the formation of the San Pedro caldera, an ∼4-km-wide subcircular depression that is today partially buried by younger volcanic products. During the second period of activity (ca. 280–30 ka), rhyolitic and dacitic domes were mostly emplaced along the caldera rim and inside the caldera. In addition, hawaiites and mugearites built the Amado Nervo shield volcano on the caldera rim. Intermediate- to high-silica lava and pyroclastic rocks are subalkaline, whereas the Amado Nervo mafic lavas are transitional toward the alkaline series (Na-alkaline). No genetic relationships have been found between subalkaline and transitional Na-alkaline rocks, which are thought to represent different batches of magma from different mantle sources. Petrographic, geochemical, and isotopic variations observed in the transitional Na-alkaline Amado Nervo lavas point to a parental magma from a mantle melt that underwent limited olivine separation during its ascent to the surface. Among subalkaline rocks, two groups showing contrasting petrographical and geochemical features are recognized based on the presence of amphibole. Amphibole-bearing intermediate to silicic rocks are characterized by lower Ce and other incompatible trace element contents and lower 87 Sr/ 86 Sr (0.70382–0.70401) compared to amphibole-free rocks (0.70411–0.70424). On the basis of petrological characteristics, the two groups of magmas are interpreted to have evolved in two different magmatic reservoirs under different pressures and water contents in the mid-upper crust. Both groups of magmas were differentiated by open-system processes. We propose that assimilation and equilibrium crystallization (AEC) processes account for the amphibole-bearing rocks. Hotter and less evolved magmas interacted to a higher degree with the crust than the more evolved and colder magmas. This produced the observed higher 87 Sr/ 86 Sr in the less differentiated rocks of the amphibole-bearing group. On the other hand, amphibole-free rocks have chemical and isotopic characteristics that can be modeled by assimilation and fractional crystallization (AFC) processes. All data suggest that the two groups of subalkaline rocks have been generated by a common parental hydrous magma, but evolved in two different reservoirs. Amphibole-bearing magmas underwent amphibole fractionation in a mid-upper crustal reservoir and show assimilation of two types of basement: one akin to Oaxaquia and another akin to the Guerrero terrane. Amphibole-free magma only shows assimilation of an Oaxaquia-type basement.