The southern Great Xing’an Range (SGXR), located in the eastern segment of the Central Asian Orogenic Belt (CAOB), is one of the most economically important Cu–Mo–Fe–Sn–Pb–Zn–Ag metallogenic provinces in China. The newly discovered Panjiaduan Cu–Pb–Zn deposit (9.3 Mt; at 1.36% Cu, 2.90% Pb, 3.80% Zn and 38.12 g/t Ag), located in the SE segment of the SGXR, is primarily hosted in fracture zones in volcanic rocks and granodiorite of the Manitu Formation. Four paragenetic stages of metallic mineralization are identified: (I) quartz-pyrite-arsenopyrite; (II) quartz-polymetallic sulphide; (III) quartz-galena-sphalerite-argentite; and (IV) quartz-calcite-minor sulphide. The hydrothermal quartz contains three types of primary fluid inclusion (FIs): vapour-rich two-phase liquid-vapour (LV-type), liquid-rich two-phase liquid-vapour (VL-type) and three-phase liquid-vapour-solid FIs (SL-type). Stages I and II contain all types with homogenization temperatures (Th) of 324–386 °C and 276–334 °C as well as salinities of 0.7–38.0 wt% and 0.9–34.7 wt%, respectively, whereas stage III is composed of VL- and LV-type FIs with Th of 210–269 °C and salinities of 0.5–7.2 wt%. Only VL-type FIs occur in stage IV, with Th of 139–185 °C and salinities of 1.6–4.2 wt%. The δ18OH2O and δD values vary from −15.7 to 2.6‰ and −132.7 to −110.2‰, respectively, indicating predominant meteoric water with an initial magmatic source. The He–Ar isotopic compositions of the pyrite inclusions from the Panjiaduan Cu–Pb–Zn veins suggest that fluids were derived from the crust.