The newly-discovered Kaladawan South Zn–Pb–Cu orefield in eastern Altyn Mountains is composed of five Zn–Pb(–Cu) deposits, with the largest one containing 414.4 thousand tonnes (kt) Zn, 265.2 kt Pb and 149.2 kt Cu. Stratiform/lenticular orebodies are hosted by the Ordovician volcanic–sedimentary sequences subjected to greenschist-facies metamorphism. Two major ore-forming stages with significant cross-cutting relationship are identified at Kaladawan South: Stage (I) of the earlier massive, banded, disseminated barite-rich sulfide ores, and Stage (II) of the later polymetallic sulfide–quartz veins with economically less importance. Fluid inclusions (FIs) locked in quartz of Stage I massive sulfide ores are homogenized completely at 226–354 °C with calculated seawater-like salinities of 2.7–4.2 wt% NaCl equiv. These characteristics of ore-forming fluids coupled with ore textures of typical VMS deposits, are interpreted to be originated from the modified seawater by sea-floor volcanic-hydrothermal activities. In compared, the Stage II FIs yielded lower homogenization temperatures ranging 251 °C–357 °C with higher salinities of 0.8–14.4 wt% NaCl equiv. Laser Raman analyses identified large amounts of CO2 ± (CH4–N2) in the hydrothermal fluids of Stage II. The δ18OH2O values (0.5–5.7‰) and δDH2O values of (−68.1‰ to −32.3‰) of Stage II quartz are plotted in the range of metamorphic fluids in the D–O isotopic diagram, which indicating that the CO2-rich and mesothermal fluids are metamorphic-derived. The phlogopite paragenetic in the Stage II polymetallic vein yielded a 40Ar/39Ar plateau age of 435.4 ± 3.9 Ma, similar to the age of the metamorphic muscovite (451.0 ± 4.1 Ma) from the ore-hosting schist. Based on the ore deposit geology, mineral assemblages and fluid geochemistry, the Kaladawan South Zn–Pb–Cu mineralization is attributed to be an Ordovician VMS-type deposit overprinted by the Silurian metamorphic fluids.