The southern margin of the North China Craton (NCC) hosts many world-class porphyry Mo and vein-type PbZn ± Ag deposits, forming an important polymetallic metallogenic belt in China, even over the world. Although the Mo and Pb-Zn ± Ag mineralization are temporarily and spatially associated with each other, their possible genetic links are still unclear. To delineate the relationships between the two types of ore mineralization, we carried out in-situ geochemical and S-Pb isotopic analyses on sulfides from the two spatially associated deposits, i.e., the Wangpingxigou Pb-Zn and Donggou porphyry Mo deposits in the ore district. Based on field and microscopic observations on the crosscutting relationships of various veins and paragenetic relationships of various hydrothermal minerals, three (I–III) and four (I–IV) stages of hydrothermal veins have been identified in the Wangpingxigou and Donggou deposits, respectively. Pyrite grains from stage II of the Wangpingxigou deposit have high Co/Ni ratios (mostly > 1) and Au and As contents similar to those of typical epithermal systems. Moreover, sulfides from this deposit have in-situ 206Pb/204Pb (17.345–17.417), 207Pb/204Pb (15.454–15.514), and 208Pb/204Pb (38.138–38.364) ratios similar to those of sulfides from the Donggou deposit, indicating that the two deposits were relevant to a common source. The concentrations of many elements (i.e. Pb, Ag, Sn, Zn, Sb, Mn, Au and As) in pyrite decrease gradually from the stage II of the Wangpingxigou deposit to the stage II of the Donggou deposit, consistent with metal zonation typically observed in porphyry related metallogenic systems. Further considering similar ages of the two deposits, we propose that the Wangpingxigou Pb-Zn deposit is likely distal to the Donggou porphyry Mo system. The range of δ34S values of pyrites (7.63–8.76‰) from the stage II in the Donggou deposit is similar to those of the ancient strata (Xiong’er Group) (7.31–8.17‰) in the ore district, indicating that the sulfur in ore-forming fluids may be mainly derived from the ancient strata. However, the δ34S values (9.20–9.70‰) of Stage III sulfides in the Donggou deposit are higher than those of stage II sulfides in the Donggou deposit and stage II sulfides in the Wangpingxigou deposit (7.34–9.29‰). The different sulfur isotopic compositions may be related to varied physicochemical conditions of the ore-forming fluids. Confirmation of a Mo-Pb-Zn metallogenic system in the region provides important clues on further prospecting of Mo and Pb-Zn resources in the southern margin of the North China Craton.