The Permian manganese (Mn) ore belt lies in western South China Block, and contains many large-medium Mn deposits. However, the genesis and metallogenic mechanism of these deposits remains a matter of debate. Here we shed light on this issue based on new mineralogical, geochemical, and Sr isotope data from the Changgou Mn deposit in the Zunyi orefield (Guizhou, SW China). The Mn orebodies occur as lenses and layers, and are hosted in carbonaceous-siliceous limestone, carbonaceous mudstone, and tuffaceous claystone. The ores show a variety of structures (e.g., detrital, brecciated, massive, and banded) and complex mineral compositions (e.g., galena, sphalerite, siegenite, molybdenite, barite, rutile, and monazite). The ore samples are characterized by chalcophile and siderophile element enrichments, low Al2O3/TiO2 ratios (mean 10.36), high and varying Mn/Fe ratios (1.26-4.71), distinctly high REY (rare earth and yttrium) contents (mean 766.46 ppm), and high La/Ce (mean 1.04) and low Y/Ho (mean 28.17) ratios. The footwall and ore samples have 87Sr/86Sr ratios of 0.706897 to 0.707093. Integrated mineralogical and geochemical signatures indicate that the ore-forming fluids were most probably originated from hydrothermal activities related to early-stage Emeishan Large Igneous Province (ELIP) subaqueous volcanism. Redox proxies reveal that sedimentary conditions evolved from euxinic-anoxic (footwall deposition), through anoxic-suboxic (Mn mineralization), to oxic (hanging-wall deposition). Such changes were probably resulted from a coeval eustatic sea-level drop and enhanced seawater oxygen supply. Manganese was likely initially enriched in form of Mn2+, and subsequently precipitated with oxidation, and then transformed into Mn carbonate during sediment diagenesis. To conclude, the tectono-hydrothermal activities and major environmental redox changes led by the ELIP volcanism have provided a favorable source-migration-sink system for the Mn mineralization.