The Dafang Au-Ag-Zn-Pb deposit represents one of the typical polymetallic deposits in the Nanling Metallogenic Belt (South China). However, uncertainties persist regarding its paragenesis, ore-related alteration types, and physicochemical conditions. To address these questions, our study encompasses a comprehensive suite of field surveys, microscopic observations, Electron Probe Microanalysis (EPMA), and Laser Ablation-Inductively Coupled Plasma -Mass Spectrometer (LA-ICP-MS) analyses. Special attention is given to sphalerite compositions to provide insights into ore-forming conditions. Orebodies are present within the contact zone of the Maoershan granodiorite porphyry and carboniferous limestone. Widespread magmatic-hydrothermal metasomatism is evidenced by garnet, diopside, tremolite, actinolite, epidote, and chlorite, analogous to the globally recognized skarn systems. The sulfide stage mainly composites two substages of an earlier Fe-As-Cu and a later Zn-Pb-Sn, overprinted by a far later Au-Ag mineralization stage. Four generations of sphalerite (SpA, SpB, SpC, and SpD) with distinct ore textures and mineral assemblages were precipitated during the Zn-Pb-Sn substage. The Dafang sphalerites exhibit enrichment in two groups of trace elements: Cu, Ag, and Sn in micro-mineral inclusions, and Fe, Mn, Cd, and In incorporated into the crystal structure. LA-ICP-MS mapping and correlation analyses reveal the potential direct and coupled substitution mechanisms. Geothermometer studies indicate that the Dafang sphalerites are crystallized at a moderate to high temperature (319-410 C-degrees), corresponding to an intermediate sulfur fugacity (from -9.9 to -8.6) as shown in the logfS(2)-T phase diagram. Fluctuations of redoxsensitive elements, such as Se and Mn, suggest the gradual involvement of meteoric fluids into the skarn system, leading to a transition from reduced to oxidized. Collectively, the Dafang polymetallic deposit represents a skarn system formed under physicochemical conditions of moderate to high temperature, intermediate sulfur fugacity, and a transition from reduced to oxidized state.