The Middle-Late Jurassic Cu-Pb-Zn-bearing and W-bearing granites in the Nanling Range have distinctly different mineralogical and geochemical signatures. The Cu-Pb-Zn-bearing granites are dominated by metaluminous amphibole-bearing granodiorites, which have higher CaO/(Na2O+K2O) ratios, light/heavy rare earth element (LREE/HREE) ratios, and δEu values, lower Rb/Sr ratios, and weak Ba, Sr, P, and Ti depletions, exhibiting low degrees of fractionation. The W-bearing granites are highly differentiated and peraluminous, and they have lower CaO/(Na2O+K2O) ratios, LREE/HREE ratios, and δEu values, higher Rb/Sr ratios, and strong Ba, Sr, P, and Ti depletions. The Cu-Pb-Zn-bearing granites were formed predominantly between 155.2 and 167.0 Ma with a peak value of 160.6 Ma, whereas the W-bearing granites were formed mainly from 151.1 to 161.8 Ma with a peak value of 155.5 Ma. There is a time gap of about 5 Ma between the two different types of ore-bearing granites. Based on detailed geochronological and geochemical studies of both the Tongshanling Cu-Pb-Zn-bearing and Weijia W-bearing granites in southern Hunan Province and combined with the other Middle-Late Jurassic Cu-Pb-Zn-bearing and W-bearing granites in the Nanling Range, a genetic model of the two different types of ore-bearing granites has been proposed. Asthenosphere upwelling and basaltic magma underplating were induced by the subduction of the palaeo-Pacific plate. The underplated basaltic magmas provided heat to cause a partial melting of the mafic amphibolitic basement in the lower crust, resulting in the formation of Cu-Pb-Zn mineralization related granodioritic magmas. With the development of basaltic magma underplating, the muscovite-rich metasedimentary basement in the upper-middle crust was partially melted to generate W-bearing granitic magmas. The compositional difference of granite sources accounted for the metallogenic specialization, and the non-simultaneous partial melting of one source followed by the other brought about a time gap of about 5 Ma between the Cu-Pb-Zn-bearing and W-bearing granites.