Abstract Partial melting of the juvenile lower crust is thought to contribute to porphyry Cu formation in Tethyan collisional domains, such as Gangdese, Sanjiang, Iran. We used a Monte Carlo-based partial melting model of the eastern Gangdese lower crust based on a refined dataset of Eocene to Miocene whole-rock element and isotope geochemistry to evaluate its control on Cu endowments. Our findings agree with previous studies that multiple factors (magmatic source, oxidation state, water content, volatiles) affect the probability of depositing economic Cu. A key finding of Miocene giant to large porphyry Cu formation is a significant increase in the degree of melting of the lower crust from Eocene to Miocene, as well as a transition of the composition of the lower crustal mineral assemblages from plagioclase-dominated to amphibole- and garnet-dominated assemblages. The modeling delineates clearly the spatial variations in melting degree and mineral proportion of the lower crust source from west to east (longitude 88°–94° E), showing the tonnage of porphyry copper deposits in the eastern Gangdese belt has a positive correlation with melting degree. We suggest that the proximity to slab-tearing zones and the influx of mantle-derived trachytic magmas were instrumental in enhancing the Cu endowments. A large degree of partial melting of the lower crust with continuous amphibole fractional crystallization and mantle input results in high magmatic water content and oxidation, facilitating the mobilization and concentration of Cu within the magma, thereby enhancing the potential for porphyry deposit formation. This research not only enhances our understanding of the intricate petrogenetic mechanisms behind significant mineral deposits but also has considerable implications for future exploration in the collisional orogens.