The large-scale Bayanbaolege Ag polymetallic deposit is situated in the Tuquan–Linxi Fe-Sn-Cu-Pb-Zn-Ag metallogenic sub-belt in eastern slopes of the southern Great Xing’an Range, NE China. The sulfide-quartz vein-type orebodies in the deposit are hosted primarily in the Early Cretaceous granodiorite porphyry and Late Permian strata. Three primary paragenetic stages of veining have been identified: (I) arsenopyrite- pyrite-quartz stage, (II) pyrite-sphalerite-quartz stage, and (III) galena-silver minerals (pyrargyrite, argentite, and pearceite)-calcite stage. The Rb–Sr dating of sulfides yielded an isochron age of 129.9 ± 2.9 Ma (MSWD = 2.1) for the sphalerite, which constrains the mineralization age to the Early Cretaceous. Rb and Sr concentrations in the sulfides ranged from 0.0940 to 1.0294 ppm and 0.0950–3.3818 ppm, respectively. The initial ⁸⁷Sr/⁸⁶Sr value of the sphalerite was 0.70852 ± 0.00018, indicating that the mineralized materials were derived from the mixed crust-mantle source area. S isotope analysis showed that the δ³⁴S values of the sulfide samples varied in a narrow range, from −1.5‰ to +1.3‰ (mean −0.65‰), indicating a magmatic S source. Pb isotopic ratios of the sulfides (²⁰⁶Pb/²⁰⁴Pb = 18.306–18.416, ²⁰⁷Pb/²⁰⁴Pb = 15.524–15.605, ²⁰⁸Pb/²⁰⁴Pb = 38.095–38.479) and the granodiorite porphyry (²⁰⁶Pb/²⁰⁴Pb = 18.341–18.933, ²⁰⁷Pb/²⁰⁴Pb = 15.539–15.600, ²⁰⁸Pb/²⁰⁴Pb = 38.134–38.944) reflect that the ore-forming materials originated from contemporaneous magma with Early Cretaceous granodiorite porphyry. This study of the Bayanbaolege deposit and other hydrothermal deposits in the area provides compelling evidence that the widespread Mesozoic magmatism and mineralization in the southern Great Xing’an Range occurred in an intracontinental extensional tectonic setting, which was associated with the westward subduction of the paleo-Pacific plate.