The newly-discovered Huanaote Ag-Pb-Zn deposit, containing 1173 tons Ag with a grade of 154 g/t, is situated in the western part of the Great Xing’an Range metallogenic belt. The source of metals and the fluid evolution for this large metallogenic system are still ambiguous. Mineralized Ag-Pb-Zn veins are primarily hosted in Late Carboniferous monzogranite and Devonian slate. Three paragenetic stages of mineralization were recognized at Huanaote, including (stage I) early pyrite + arsenopyrite + quartz ± K-feldspar; (stage II) the main ore stage sulfide (sphalerite, galena, chalcopyrite and pyrite) + sulfosalt (freibergite, bournonite, wittichenite and tetrahedrite) + quartz + sericite + chlorite ± epidote ± fluorite; and (stage III) late pyrite + quartz + calcite. The homogenization temperatures of fluid inclusion assemblage for stages I and II range from 254 to 337 ℃ and 143 to 270 ℃, respectively, while the fluid salinity varied from 2.3 to 14.2 and 0.9 to 11.8 wt% NaCl equiv. for stages I and II, respectively. The fluid δ18OH2O and δDH2O values range from −0.4 to +6.2‰ and −116.8 to −104.8‰, respectively, indicating that the source of the fluids was primarily derived from a magma with less contribution from meteoric waters. Sulfur isotope analyses of sulfides exhibit δ34S values from −4.3 to +8.0‰, consistent with those observed in other Ag-Pb-Zn deposits in this region, suggesting the sulfur was mainly magmatic origin with minor sedimentary sulfur addition. Similarly, the Pb isotope compositions of sulfides resemble those of local Mesozoic magmatism, implying a Mesozoic magmatic source for the metals. Additionally, the noble gas isotope compositions, specifically the 3He/4He ratios (ranging from 4.41 to 7.18 Ra, mean of 5.56 Ra) for fluid inclusions,strongly support a deep magmatic fluid responsible for the formation of Huanaote deposit. Fluid cooling, mixing with meteoric waters and dilution are suggested to be important processes for Ag-Pb-Zn deposition at Huanaote.