The Weiquan Ag–polymetallic deposit is located on the southern margin of the Central Asian Orogenic Belt and in the western segment of the Aqishan–Yamansu arc belt in East Tianshan, northwestern China. Its orebodies, controlled by faults, occur in the lower Carboniferous volcano-sedimentary rocks of the Yamansu Formation as irregular veins and lenses. Four stages of mineralization have been recognized on the basis of mineral assemblages, ore fabrics, and crosscutting relationships among the ore veins. Stage I is the skarn stage (garnet + pyroxene), Stage II is the retrograde alteration stage (epidote + chlorite + magnetite ± hematite ± actinolite ± quartz), Stage III is the sulfide stage (Ag and Bi minerals + pyrite + chalcopyrite + galena + sphalerite + quartz ± calcite ± tetrahedrite), and Stage IV is the carbonate stage (quartz + calcite ± pyrite). Skarnization, silicification, carbonatization, epidotization, chloritization, sericitization, and actinolitization are the principal types of hydrothermal alteration. LA–ICP–MS U–Pb dating yielded ages of 326.5±4.5 and 298.5±1.5 Ma for zircons from the tuff and diorite porphyry, respectively. Given that the tuff is wall rock and that the orebodies are cut by a late diorite porphyry dike, the ages of the tuff and the diorite porphyry provide lower and upper time limits on the age of ore formation. The δ13C values of the calcite samples range from ?2.5‰ to 2.3‰, the δ18OH2O and δDV-SMOW values of the sulfide stage (Stage III) vary from 1.1‰ to 5.2‰ and ?111.7‰ to ?66.1‰, respectively, and the δ13C, δ18OH2O and δDV-SMOW values of calcite in one Stage IV sample are 1.5‰, ?0.3‰, and ?115.6‰, respectively. Carbon, hydrogen, and oxygen isotopic compositions indicate that the ore-forming fluids evolved gradually from magmatic to meteoric sources. The δ34SV-CDT values of the sulfides have a large range from ?6.9‰ to 1.4‰, with an average of ?2.2‰, indicating a magmatic source, possibly with sedimentary contributions. The 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of the sulfides are 17.9848–18.2785, 15.5188–15.6536, and 37.8125–38.4650, respectively, and one whole-rock sample at Weiquan yields 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of 18.2060, 15.5674, and 38.0511, respectively. Lead isotopic systems suggest that the ore-forming materials of the Weiquan deposit were derived from a mixed source involving mantle and crustal components. Based on geological features, zircon U–Pb dating, and C–H–O–S–Pb isotopic data, it can be concluded that the Weiquan polymetallic deposit is a skarn type that formed in a tectonic setting spanning a period from subduction to post-collision. The ore materials were sourced from magmatic ore-forming fluids that mixed with components derived from host rocks during their ascent, and a gradual mixing with meteoric water took place in the later stages.