Melt inclusions in phenocrysts from Volcán Popocatépetl and Volcán de Colima within the Trans Mexican Volcanic Belt (TMVB) are dacitic to rhyolitic. Trends in melt inclusion major element and water concentrations form the evolved extension of other Mexican volcanics including those presumed to be derived directly from primitive melts. Water concentrations in Popocatépetl and Colima melt inclusions are similar (0.3 to 3.4 wt.% H2O). Melt-vapor equilibration pressures calculated from dissolved H2O and CO2 (Popocatépetl) or H2O (Colima) in melt inclusions correspond to depths of entrapment of 12 km or less. Water and carbon dioxide concentrations correlate negatively with SiO2 and potassium. Normalized olivine–augite–quartz compositions are consistent with near cotectic crystallization under vapor-saturated conditions at pressures of 1.5 kb or less. Our results show that Popocatépetl and Colima magmas have undergone vapor-saturated crystallization during ascent in conjunction with varying degrees of mixing between degassed rhyodacitic and less degassed, mafic melts in the upper portions of the crust. These data suggest melt evolution occurred in conduits or inter-fingered dikes rather than a large stratified magma chamber.