The large-scale Qixiashan Pb-Zn Deposit in the east Middle-Lower Yangtze metallogenic belt is hosted in carbonate rocks. Based on a detailed mineral paragenesis study, in-situ LA-ICP-MS (laser ablation inductively coupled plasma mass spectrometer) trace element geochemistry data for pyrite and sphalerite from different stages in the Qixiashan Deposit are reported, the Pb-Zn mineralization processes are reconstructed, and a genetic model is constructed. Four paragenetic stages of Pb-Zn ore deposition are identified: the biogenic pyrite mineralization stage (Stage 1), the early stage of hydrothermal Pb-Zn mineralization (Stage 2), the late stage of hydrothermal Pb-Zn mineralization (Stage 3), and the carbonate stage (Stage 4). Stages 2 and 3 are the main ore stages. The trace element characteristics of the sulfide in stages 2 and 3, such as the higher Co/Ni and lower trace element contents of the pyrite and the Fe, Mn, and Ge contents of the sphalerite, indicate that they were generated by magmatic-hydrothermal processes. Furthermore, the lower Cu, Ag, Sb, and Pb contents of the pyrite and sphalerite of Stage 3 compared to Stage 2 suggest an increase in magmatic-hydrothermal activity from Stage 2 to Stage 3. The hydrothermal fluids leached trace elements (e.g., Cu, Ag, Sb, and Pb) from the previously deposited primary pyrite and sphalerite, which were precipitated in the later hydrothermal stage Cu, Au, Ag, Sb, and Pb bearing minerals and secondary pyrite and sphalerite with lower trace element contents (e.g., Cu, Au, Ag, Sb, and Pb). Compared with the pyrite from stages 2 and 3, the Stage 1 pyrite has relatively higher trace elements contents (Sb, Cu, Zn, Au, Ag, Pb, As, and Ni). However, their lower Co/Ni ratio suggests a syngenetic sedimentary origin. Based on the petrographic features and trace element data, a multi-stage mineralization model is proposed. The Stage 1 biogenic pyrite formed stratiform pyrite layers, which provided reducing conditions and a base for the subsequent Pb-Zn mineralization. During Stage 2, subsequent hydrothermal fluid interacted with the stratiform pyrite layers, which resulted in sulfide precipitation and the formation of stratiform Pb-Zn orebodies. In Stage 3, the hydrothermal fluid replaced the limestone along the fractures, which triggered the formation of Pb-Zn vein orebodies.