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The Zhifang Mo deposit is located in the northeastern Qinling Orogen along the southern margin of the North China Craton. The deposit represents a quartz-vein system hosted in the Mesoproterozoic Xiong'er Group volcanic rocks. We identify three hydrothermal stages (early, middle and late), characterized by veinlets of quartz–pyrite, quartz–molybdenite–pyrite–chalcopyrite–galena–sphalerite, and quartz–carbonate assemblages, respectively. Five molybdenite samples from the Zhifang deposit yield Re–Os ages ranging from 241.2 ± 1.6 Ma to 247.4 ± 2.5 Ma, with an isochron age of 246.0 ± 5.2 Ma (2σ, MSWD = 7.4), and a weighted mean age of 243.8 ± 2.8 Ma (2σ, MSWD = 5.5). The Re–Os age shows that the Mo mineralization occurred during the Indosinian Orogeny, and suggests that the mineralization is unrelated to the Yanshanian magmatism or the Paleo-Mesoproterozoic volcanic–hydrothermal event. This study also reports a new Sr–Nd–Pb isotope dataset from ore sulfides in an attempt to constrain the source of the ore-forming fluids. Ten sulfide samples from middle stage of the Zhifang Mo deposit yield I Sr (t) ratios of 0.710286–0.711943, with an average of 0.711004; ε Nd (t) values between − 19.5 and − 14.8, with an average of − 16.7; and ( 206 Pb/ 204 Pb) i , ( 207 Pb/ 204 Pb) i and ( 208 Pb/ 204 Pb) i ratios of 17.126–17.535, 15.374–15.466 and 37.485–37.848, with averages of 17.380, 15.410 and 37.631, respectively. One pyrite from the early stage yield I Sr (t) of 0.722711–0.722855, with an average of 0.722783, which is higher than those of the middle stage sulfides and suggests equilibration with wallrocks. The ε Nd (t) values are in the range of − 17.3 to − 16.6 with a mean at − 17.0; and ( 206 Pb/ 204 Pb) i , ( 207 Pb/ 204 Pb) i and ( 208 Pb/ 204 Pb) i ratios are 17.386, 15.405 and 37.622, respectively. The ore sulfides show higher Pb-isotope ratios, higher ε Nd (t) and lower I Sr (t) values than the host rocks. The results suggest that the ore-forming fluids had lower I Sr (t), and higher ε Nd (t) values than the ore sulfides, and were possibly sourced from the Dengfeng Complex. The southward subduction of the North China Craton beneath the Huaxiong Block during the Triassic was possibly responsible for the formation of the Waifangshan orogenic Mo system. [ABSTRACT FROM AUTHOR]