The Xiaoliugou W–Mo ore field lies within the mid-Paleozoic North Qilian Orogen, NW China, and hosts a W resource of 48.8 Mt @ 0.4% and 412.6 Mt of Mo @ 0.075%. It contains five deposits, including Xiaoliugou, Qiqing, Guishan, Qibao and Shiji. The main mineralization styles at Xiaoliugou are skarn and veins in which the mineral sequence is scheelite > molybdenite > chalcopyrite and occurs in the endo- and exo-contact zones of granite intrusions. The scheelite-dominated orebodies are overprinted by molybdenite-dominated quartz veins. Two molybdenite samples yielded Silurian Re–Os model ages of 427.4 ± 6.0 Ma and 428.2 ± 6.0 Ma. Three muscovite samples coexisting with molybdenite yielded Middle Devonian Ar–Ar ages of 392.0 ± 2.7 Ma, 391.1 ± 2.7 Ma and 391.4 ± 2.8 Ma. The Re–Os and Ar–Ar ages indicate that the W–Mo mineralization and alteration occurred at ca. 428–391 Ma, which corresponds with regional continental collision within the Qilian Orogen. δ34S for the sulfides molybdenite and pyrite are 7.70–11.67‰ and 4.98–13.17‰, respectively. The 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb of the sulfides are 17.98–21.73, 15.34–18.81, and 37.18–38.63, respectively. The granites yield similar corrected (206Pb/204Pb)i, (207Pb/204Pb)i and (208Pb/204Pb)i, ranging 16.14–19.35, 15.44–15.63, and 37.41–38.31, respectively. We calculated δ18O of the fluid inclusions in quartz range from − 3.38–2.34‰, whereas the δD of the hydrothermal fluids ranges from − 94 to − 47‰. The S-, Pb-, O- and D-isotopic data imply that the metals originated from the granite intrusion with a minor component sourced from the host sediments, and that the ore-forming fluids were dominated by magmatic-hydrothermal fluids mixed with minor meteoric water.