We present a comprehensive petrologic study of lower-crust mafic and felsic xenoliths hosted by Quaternary alkaline basalts of the Valle de Santiago monogenetic volcanic field. This is the only locality along the entire Trans-Mexican volcanic belt where the abundance and size of xenoliths allow the understanding in great detail of processes associated with interactions of young subduction-related magmatism and the deep continental crust. Mafic xenoliths (two pyroxene ± spinel granulites and metanorthosites), olivine-rich gabbroic xenoliths, and transitional xenoliths compose the bulk of the population, although a few belong to the charnockitic suite (enderbite and faersundite). Thermobarometric calculations (two-pyroxene, ilmenite-magnetite, Ti-in amphibole, amphibole-plagioclase, and phase equilibria in the system NCMAS (Na-Ca-Mg-Si)) result in pressures around 9 kbar and temperatures of 1000–1100 °C for the granulite-facies metamorphism, which would give a very hot lower crust, ∼33 km thick, beneath Valle de Santiago and a mean geothermal gradient of ∼30 °C/km. Igneous zircons (Th/U = 0.03–0.87) extracted from one of the felsic granulites yielded a major peak of latest Cretaceous age (67.1 Ma), interpreted as the crystallization age of the granitic protolith, without inheritance from Precambrian or Paleozoic crust. Minor peaks at 45.1 and 25.5 Ma are interpreted as partial Pb losses from some of the Cretaceous zircons. Trace-element geochemistry, as well as Sr, Nd, and Pb isotopic studies performed on two granulites, is consistent with the juvenile and coeval nature of both the mafic metagabbroic xenoliths and the alkaline basaltic magmas that lifted the xenoliths from the lower crust. Two intermediate stages in the thermal evolution of the sampled xenoliths include the emplacement at different depths of volatile and K-Fe-Ti–rich oxidized melts represented by igneous assemblages with kaersutite, biotite, titanomagnetite, spinel, plagioclase, Fe-rich epidote, clinopyroxene, fayalitic olivine, and glasses that pervasively invaded most granulite xenoliths before being taken to the surface. A preferred plumbing system model is presented depicting a protracted Miocene to Quaternary basaltic intraplate magmatic system that sampled former basaltic batches stationed in the lower crust, together with the Late Cretaceous deep-seated granitoids beneath Valle de Santiago in the backarc of the central Trans-Mexican volcanic belt. Both components were later subjected to granulite-facies conditions in the lower crust, most probably related to the continued heating of the crust by basaltic magmas underplated in the central Trans-Mexican volcanic belt backarc region.