Display omitted •Two groups of granitoids are differentiated: A1-type alkaline (180–160 Ma) and A2-type aluminous (160–150 Ma).•Group 1 magmas underwent crust–mantle interaction and contributed to the Cu-Mo mineralization.•Group 2 magmas experienced strong magmatic differentiation, resulting in W-Sn mineralization.•Group 1 granitoids have fast cooling and uplift rates, Group 2 granites received upper crustal contamination.•A comprehensive model of “centralized mantle upwelling & gradational crustal extension” is proposed. The central Nanling region in South China was the site of uplift, extensional deformation, granite magmatism and hydrothermal activity from 180 to 150 Ma. Information on the age, petrological characteristics, major and trace element contents, whole rock Sr and Nd and zircon Hf isotopic compositions of granitic plutons were synthesized to constrain the sources, evolutionary processes, and uplift-cooling rates of intrusions that host Cu–Mo and W–Sn deposits in this region. The older (180–160 Ma) Cu–Mo related granitoids are less differentiated, A1 type alkaline rocks with faster cooling and uplift rates. They have younger Nd and Hf two-stage model ages and higher εNd(t) and εHf(t) values that indicate mantle derived magmas were moderately contaminated by upper crust. The younger (160–150 Ma) W–Sn related granites are more differentiated, A2 type aluminous rocks with slower cooling and uplift rates. They have older Nd and Hf two-stage model ages and lower εNd(t) and εHf(t) values that require more upper crustal contamination. The time–space distribution and characteristics of these granitoids and ore deposits are indicative of centralized mantle upwelling and gradational crustal extension. The older rapidly-uplifted, less contaminated granitoids with Cu–Mo mineralization occur near the center of an intra-continental extension bulge produced by mantle upwelling, whereas the younger, slowly-uplifted, more contaminated granitoids with W–Sn mineralization occur on the periphery. The results suggest that metals in the Cu–Mo deposits may have come from the mantle whereas those in the world-class Nanling W–Sn polymetallic deposits were derived from Early Mesoproterozoic (1.4–1.6 Ga) crustal basement of the Cathaysia Block in South China.