The Dengfuxian and Xitian ore fields, located in the central Nanling Range of South China, are characterized by multi‐stage W–Sn polymetallic mineralization. In this study, whole‐rock and zircon compositions in altered granites from four typical deposits in these ore fields (i.e., Dalong Pb–Zn, Xiangdong W, Gaolong fluorite, and Shaiheling Sn–Pb–Zn) were studied to constrain their fluid chemistry and mineralization history. Compared to unaltered granites at Dengfuxian and Xitian, these fluid‐altered granites are characterized by more variable SiO2 (64.2–78.4%) and lower TiO2 (0.02–0.12%), CaO (0.25–1.2%), and Na2O (0.31–2.6%) concentrations, lower ΣREE (87–156 ppm), and higher Zr/Hf (11.1–31.6) and Y/Ho (31.1–53.4) ratios, suggesting intense F‐rich fluid metasomatism. Zircon cathodoluminescence (CL), transmitted light and back‐scattered electron (BSE) imaging, laser ablation multi‐collector inductively coupled plasma mass spectrometry (LA‐MC‐ICP‐MS) trace‐element analysis, U–Pb dating, and Hf isotopes revealed a sequence of three W–Sn polymetallic mineralization stages: a Triassic stage (~220 Ma), a Jurassic stage (~150 Ma), and a Cretaceous stage (~80 Ma). The Triassic episode was associated with a highly fractionated granitic magma derived from the lower crust and contaminated by basement rocks; the magmatic fluid was affected by a high 176Hf/177Hf component from the ~770‐Ma basement and probably precipitated under high F and high fO2 conditions. The Jurassic episode was related to mantle–crust interaction and resulted in large‐scale W–Sn mineralization at decreased fO2. The Cretaceous episode was marked by Sn mineralization in a lithospheric extensional setting. We infer that basement rocks were the major source of metals for the world‐class W–Sn ore deposits in the Nanling Range of South China. This study also demonstrates that whole‐rock geochemistry of hydrothermally altered granites in combination with Lu–Hf isotopic, U–Pb dating, and trace element analyses of magmatic and hydrothermal zircons can be a useful approach to recognition of multi‐stage magmatic and mineralization processes.