The Dongtangzi large Zn-Pb deposit is located in the southwest of the Fengxian-Taibai (abbr. Fengtai) ore cluster in the west Qinling orogen, whose origin has been controversial, positing diverse genesis mechanisms such as sedimentary-exhalative (SEDEX), sedimentary-reformed, and epigenetic hydrothermal type. In this work, based on detailed observation and systematic study on ore geology, the results of high-precision Rb-Sr isotopic dating on sulfides of the main orebody and Sm–Nd isotopic dating on associated carbonates have been carried out, which yield isochron ages of 211.6 ± 2.6 Ma and 211 ± 4 Ma, respectively. In-situ S-Pb isotopic studies show that the ore related sulfides display a narrow range of δ34S values from 1.1 ‰ to 10.2 ‰, with 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb ratios of 18.07 to 18.27, 15.64 to 15.66, and 38.22 to 38.76, respectively. While the pyrite of sedimentary period and the granite porphyry dike have δ34S values vary from 15.8 to 21.4‰, and from 2.1 to 4.3‰ (with 206Pb/204Pb ratios of 18.09 to 18.10, 207Pb/204Pb ratios of 15.59 to 15.61, and 208Pb/204Pb ratios of 38.17 to 38.24) respectively. Combining the regional geology, we propose that the Dongtangzi Zn-Pb deposit is the product of multi-stage epigenetic hydrothermal fluid processes, driven by late Triassic regional tectono-magmatic activities in regional extensional regime, with metallic materials originate from a mixture of Triassic magmatic processes and metamorphic basement.