Economically important porphyry Cu-Mo deposits (PCDs) are generally hosted by upper crustal plutons of variable chemical compositions related to distinct geodynamic settings. The absolute timing and duration of pluton assembly and PCD formation are critical to understanding the genetic relationship between these interrelated processes. Here, we present new comprehensive zircon U-Pb and molybdenite Re-Os ages that tightly constrain the timing and duration of pluton assembly and the age of mineralization in one of the largest ore-bearing plutons of the central Tethyan metallogenic belt, the Meghri-Ordubad pluton, southern Armenia and Nakhitchevan, Lesser Caucasus. This composite pluton was incrementally assembled during three compositionally distinct magmatic episodes over ~30 m.y., comprising Middle Eocene (48.9–43.1 Ma) calc-alkaline subduction-related magmatism lasting 5.8 ± 0.8 m.y., followed by postsubduction Late Eocene–Middle Oligocene (37.8–28.1 Ma) shoshonitic magmatism over 9.7 ± 0.9 m.y., and Late Oligocene–Early Miocene (26.6–21.2 Ma) adakitic magmatism consisting of shoshonitic dikes and high-K calc-alkaline granodioritic magmas emplaced over 5.4 ± 0.4 m.y. Despite the distinct geodynamic settings and magma compositions, each intrusive suite culminated in the formation of variably sized PCDs, including the giant Oligocene Kadjaran porphyry Cu-Mo deposit associated with high-Sr/Y shoshonitic magmas. Complementary in situ zircon hafnium (eHfzircon = +8 to +11.3) and oxygen (d18Ozircon = +4.6‰ to +6.0‰) isotope data support a mantle-dominated magma source with limited crustal contribution and/or cannibalization of young and juvenile lower-crustal cumulates. We conclude that, independent of geodynamic setting and magma composition, long-lived (5–10 m.y.) incremental mantle-derived magmatism is a prerequisite to form fertile magmatichydrothermal systems, and especially giant PCDs.