This study investigates the temporal relationships between mineralization and magmatism in the Khatoon-Abad porphyry Mo-Cu prospect (Urumieh-Dokhtar Magmatic Arc, NW Iran). Integrated zircon U-Pb and molybdenite Re-Os dating document a prolonged stationary magmatism, spanning ∼ 45 Myr (from ∼ 66 to ∼ 21 Ma; Paleocene-Early Miocene). Three main Oligocene ore-bearing granitic intrusions and an early Miocene barren dyke swarm are documented, with the main mineralization formed at ∼ 27 Ma, as attested by the molybdenite Re-Os age of 26.75 ± 0.14 Ma and the zircon U-Pb age 26.93 ± 0.30 Ma from the host granodiorite porphyry. Despite having similar geochemical fingerprints, including an adakitic signature and having REE patterns similar to productive magmas, the subsequent Oligocene granite bodies (∼26.0–25.7 Ma) yielded lower Mo-Cu enrichments and the early Miocene rhyodacite dykes (∼21 Ma) are barren. This evidence demonstrates that the efficiency of mineralization has been reduced by changes in the physiochemical conditions of magmatic-hydrothermal systems over time. We suggest that a perturbed geothermal gradient during later Oligocene granite (at ∼ 26 Ma) caused slow cooling/degassing of the melts, and hence determined an inefficient mineralization environment. We also infer that during the latest granite porphyry pulse (∼25.7 Ma), the structurally-controlled emplacement at shallower levels resulted in rapid melt cooling along with more meteoric water mixing, eventually minor potassic but vast phyllic alterations, and hence, causing a dispersed mineralization rather than a focused fluid flow. Therefore, the later Oligocene and early Miocene magmatic pulses degraded the early mineralization. The results of this study emphasize that a consistent magma supply into the chamber followed by a rapid magma-fluid flux to the mineralization site are needed for efficient mineralization in collisional settings. Otherwise multiple mineralization pathways and sites would result in low-grade ore bodies.