The Banxi Sb deposit is located in the world-class central-western Hunan Sb belt in South China, with quartz-vein type Sb-only mineralization hosted by Neoproterozoic epimetamorphic clastic sedimentary rocks. In this contribution, microthermometric, Rb–Sr geochronological and H–O isotopic analyses on fluid inclusions trapped in quartz, S isotopic studies on stibnite, and major-trace elemental measurements on fluid-altered and unaltered wall-rocks are presented to constrain the genesis of the deposit. The fluid inclusions are characterized by low homogenization temperature (170–260 °C) and low salinity 3–7 wt% NaCl equiv., with a low fluid density of 0.72–0.93 g/cm3 and a pH of 5.59. The low δDw (fluid δ2H, –140‰ to –107‰) whereas positive δ18OV-SMOW (15.9–17.2‰) and δ18Ow (fluid δ18O, 5.9–8.4‰) values in quartz indicate that the mineralizing fluid was generated from the low-grade metamorphic basement rocks and received a certain input of meteoric water. The Rb–Sr isotopic compositions of quartz samples yielded an isochron age of 196 ± 4 Ma (1σ, MSWD = 0.70) for quartz-stibnite ores. A highly radiogenic 87Sr/86Sr value (0.72663–0.74002, initial 87Sr/86Sr = 0.72640) indicates that ore-forming materials are derived mainly from basement rocks, and a direct material contribution from local granitic rocks can be ruled out. The δ34SV-CDT values of stibnite range narrowly from 4.81‰ to 6.72‰ and are in the δ34SV-CDT range of the metamorphic rocks, indicating that the sulfur was sourced from the basement rocks by sulfate reduction. Compositional differences between fluid-altered (decolorized) and unaltered wall-rocks are obvious: the migrated SiO2, SO3, LREE, Hf, Nb, Zr, Ta, Th, U, Mo, Sn, W into altered wall-rocks suggests a deep basement metamorphic rocks-derived Si-rich alkaline brine for the fluid-rock interaction; while the leached Fe2O3, MgO, MnO, TiO2, Ba, Cs, Rb, As, Co, V, Ni, Sb, Sc, Cu, Pb and Zn from the altered rocks imply a material contribution of Banxi Group wall-rocks during the Sb mineralization process. Consequently, we conclude that the quartz-stibnite stage of the Banxi Sb deposit was formed during the Late Triassic orogeny in the Xuefeng Mountain region. Heated by granitic magmatism, Sb and S were leached from the basement rocks, forming an initial Si-rich and alkaline ore-bearing fluid. Precipitation of stibnite from the fluid resulted from interacting with wall-rocks and mixing of meteoric water, coupled by releasing of stress, decreasing of temperature and lowering of the pH at higher crustal levels.