The Nanling mineralization belt, South China, is well-known for widespread W-, Sn (—W), and Cu-polymetallic ore deposits. At present, how to better trace their magma sources and constrain their magmatic processes is currently a conundrum. As a resistant mineral, apatite has shown great potential in metallogenic studies. In this study, we present a comprehensive investigation of apatite from the Baoshan (BS) and Tongshanling (TSL) Cu-bearing granites, the Wangxianling (WXL) W-bearing granite, and the Qitianling (QTL) Sn-bearing granite in South Hunan, to trace the nature of parental magma and to establish apatite discrimination criteria to be used in regional prospecting. The U-Pb age dating of apatite indicates that these different types of ore-bearing granites were all formed in the Middle-Late Jurassic. The εNd(t) values results suggest that (1) Cu-bearing granites in the Nanling Range were formed by melting of meta-igneous rocks in the deep crust, (2) W-bearing granitic magmas were generated by melting of old continental crust, while (3) Sn-bearing granitic magmas were produced by melting of crust material with various input of mantle-derived components. Apatite from the BS and TSL plutons exhibits lower F/Cl ratios compared to those from WXL, and QTL plutons, with higher Cl contents in the BS and TSL plutons, implying that the crustal basement of the suture zone was metasomatized by a Cl-enriched fluid. We used a partial least squares discriminant analysis (PLS-DA) of trace element data in apatite to differentiate Cu-, W-, and Sn (—W)-bearing plutons. We find that the most influential elements for classification are Sr, Eu, Ga, Nd, and Li. Trace elements differences reveal distinguished degrees of fractionation, and redox conditions for different types of ore-bearing granites. A comparative study of apatite from different ore-bearing granites indicates that, apatite can be a useful mineral exploration tool to differentiate Cu-, W-, and Sn (—W)-bearing plutons in the Nanling Range and South China.