Abstract The Oligocene Latir magmatic center in northern New Mexico is an exceptionally well exposed volcano-plutonic complex that hosts a variety of magmatic-hydrothermal deposits, ranging from relatively deep, F-rich porphyry Mo mineralization to shallower epithermal deposits. We present new whole-rock chemical and isotopic data for plutonic rocks from the Latir magmatic center, including extensive sampling of drill core samples of intrusive rocks from the Questa porphyry Mo deposit. These data document temporal chemical trends of porphyry-related mineralization that occurred after caldera-forming magmatism and during postcaldera batholith assembly. Silicic magmas were generated multiple times throughout the history of the Latir magmatic center, but few are associated with the formation of a mineral deposit. Whole-rock trace element ratios and Sr, Nd, and Pb isotope compositions vary throughout the protracted history of silicic magmatism. The caldera-forming ignimbrite and early phase of postcaldera intrusions are unmineralized, more enriched in high field strength elements, and generally contain less radiogenic Sr and Pb and more radiogenic Nd than later intrusions. The Questa porphyry Mo deposit formed immediately after the most isotopically primitive phase of the batholith was assembled, ruling out simple reworking of juvenile mantle-derived crust as the source for mineralizing magmas. Rhyolite dikes associated with polymetallic sulfide deposits intruded ~800 k.y. after Mo mineralization, and Nd isotope data indicate that these dikes are associated with different batches of magma and are unrelated to the Mo-mineralizing intrusions at the Questa mine. Together, these data indicate that the source of magmas changed significantly throughout the 10-m.y. history of the magmatic center. We assess multiple genetic models for porphyry-related magmatism against this data set, favoring models with discrete periods of magma genesis from a deep hybridized zone in the lower crust giving rise to the punctuated periods of mineralization. These observations suggest that the formation of mineral deposits within a central magmatic locus is likely the result of the piecemeal assembly of individual hydrothermal-magmatic systems, and that distal and younger polymetallic mineralization commonly observed near known porphyry deposits represents decoupled processes.