The southern Great Xing'an Range (SGXR) is one of the most important metallogenic belts in Northeast China, containing numerous deposits of Cu, Fe, Pb, Zn, Au, etc. The newly discovered Shenshan Fe–Cu skarn deposit, located in the northern segment of the SGXR, is spatially and temporally associated with Mesozoic granodiorites that were emplaced into the Zhesi Formation. Based on field investigations and petrographic observations, four main paragenesis stages of skarn formation and ore deposition have been distinguished: garnet–diopside (Stage I), magnetite–quartz (Stage II), pyrite–chalcopyrite–molybdenite–quartz (Stage III), and barren sulphide–quartz–carbonate (Stage IV). Stage I is characterized by the formation of garnet and diopside and high-temperature (365–495 °C) hypersaline (37.56–49.8 wt% NaCl equiv.) hydrothermal fluids with a fluid inclusion (FI) assemblage of daughter-mineral-bearing three-phase (SL-type), liquid-rich (VL-type), and vapour-rich (LV-type) FIs. These fluids were most likely generated directly from a silicate melt due to the boiling of primary magmatic fluids at a depth of ~1 km, at a lithostatic pressure of 300 bars. Stage II coincides with the replacement of garnet and diopside by tremolite, quartz and magnetite. Associated hydrothermal fluids are preserved in coexisting VL- and LV-type FIs and are characterized by δD and δ18OH2O values in a narrow range (−87.2‰ to −85.3‰ and 7.6‰ to 8‰, respectively) and lower fluid salinity and temperature than Stage I. This suggests that the Fe-mineralization-related fluids also evolved by the boiling of magmatic brine. Stage III is characterized by the growth of pyrite, chalcopyrite, and molybdenite. The hydrothermal fluids of this stage are also represented by VL- and LV-type FIs that yield low temperatures (223–350 °C) and low salinities (0.7–13.4 wt%). These fluids yield lower δD values (−113.6‰ to −108.7‰) that indicate the Stage III fluids originated from the mixing of magmatic brine with meteoric water. Stages II and III are the main ore-forming stages in the Shenshan deposit. The sulfur isotope (δ34S) concentrations of Stage III sulphides cover a narrow range of −5.54‰ to +0.1‰ (mean = −1.75‰), indicating a magmatic source. Based on the fluid inclusion and stable isotopic data, it is concluded that the fluids of the main ore-forming stage evolved by the boiling of magmatic fluids at a depth of ~1 km and hydrostatic pressure of ~100 bars. Only VL-type FIs are observed in Stage IV; these fluids yield the lowest homogenization temperatures (120–217 °C) and lowest salinities (5.7–9.9 wt%). The results of fluid inclusion and H–O isotopic analyses indicate that the ore-forming fluids evolved from a magmatic fluid in Stages I and II to a lower-temperature and lower-salinity meteoric water during Stages III and IV. Boiling is considered an important mechanism of extensive metal precipitation in the Shenshan Fe–Cu deposit. Lead isotope values (206Pb/204Pb = 18.195–18.352, 207Pb/204Pb = 15.519–15.532, 208Pb/204Pb = 38.072–38.11) also suggest that the ore materials in the hydrothermal fluids were derived from magmas. Taken together, the geology, mineralogy, fluid inclusion, and H–O–S–Pb isotopic characteristics of the Shenshan deposit confirm that it is a typical contact metasomatic skarn deposit.