The Wulasigou polymetallic (zinc–copper–iron–gold) deposit is located in the volcano–sedimentary Kelan Basin of the Chinese Altay. The orebodies of the Wulasigou polymetallic deposit are hosted in the second unit of the upper member of the Lower Devonian Kangbutiebao Formation and exhibit the characteristics of a stratabound deposit. Three mineralization periods are identified: an exhalative–sedimentary period, a regional metamorphism period, and a supergene period. The exhalative–sedimentary period is the main mineralization period and can be subdivided into stage 1 (the pyrite–magnetite stage), stage 2 (the pyrite–sphalerite–magnetite stage), and stage 3 (the pyrite–chalcopyrite–native gold stage). Zircon U–Pb dating of a metamorphic volcanic tuff from the second unit of the upper member of the Kangbutiebao Formation yields an age of 397.9 ± 2.8 Ma, consistent with the mineralization age (391.3±2.7 Ma), indicating that the orebodies and the host rocks share close spatial and temporal relationships and are genetically related. Liquid-rich biphase (L type) fluid inclusions are the most common type in the quartz and calcite samples from every stage of the exhalative–sedimentary period. The ore-forming fluids of the exhalative–sedimentary period homogenize at 564–120 °C and are of moderate to low salinity (17.61–0.71 wt% NaCl equiv). The quartz and magnetite samples from stage 1 of the exhalative–sedimentary period yield δ¹⁸O_H2O concentrations ranging from 0.9‰ to 6.1‰ and from 8.3‰ to 9.7‰, respectively, and δD values that range from −110.1‰ to −104.5‰ and from −123.1‰ to −113.8‰, respectively. The δ¹⁸O_H2O values for the quartz samples from stages 2 to 3 of the exhalative–sedimentary period are 2.1‰ and −1.5 to 4.0‰, respectively, and the δD values for stages 2 and 3 are −104.6‰ and −107.3‰ to −95.4‰, respectively. The fluid inclusions in pyrite yield ³He/⁴He ratios clustering within a small range from 0.53 to 0.89 Ra, ⁴⁰Ar/³⁶Ar ratios between 444.6 and 656.5, and the percentage of radiogenic ⁴⁰Ar (⁴⁰Ar*) in the range of 33.54% to 54.99%. The combined fluid inclusion studies and their H–O–He–Ar isotopic compositions show that the ore-forming fluids belong to a simple H₂O–NaCl system and have a dominantly magmatic signature mixing with an increasing seawater component vertically upward from the volcanic conduit towards the sea floor. The δ¹³C_PDB values and δ¹⁸O_SMOW values of four calcite samples from the marble vary between −1.6‰ and 0.1‰ and between 9.4‰ to 10.1‰, respectively. Calcite samples from the sulfide–(quartz) –calcite veins have δ¹³C_PDB values and corresponding δ¹⁸O_SMOW values of −6.3‰ to −3.9‰ and 8.6‰ to 9.4‰, respectively. The δ³⁴S values of the sulfides exhibit a narrow range from −4.41‰ to 4.20‰, similar to most VMS deposits. These isotopic data suggest that the ore-forming materials of the Wulasigou deposit may have been derived from both a direct deep magma source and leaching of volcanic rocks, with a larger contribution made by the magma source. The Wulasigou polymetallic deposit belongs to the volcanogenic massive sulfide (VMS)-type, and a genetic model is proposed to explain the development of the Wulasigou polymetallic deposit.