Chapai deposit is a special medium-sized carbonate-hosted Zn-Pb deposit (4.27Mt of sulfide ore with 8.15 % Zn, 3.44 % Pb, and 53.39 g/t Ag, as well as 0.82Mt of oxidized ore with 2.8 % Zn and 1.2 % Pb and 27.68 g/t Ag) with upper oxidized ore and lower sulfide ore of South China. Due to the shortage of detailed geological and geochemical constraints, the ore genesis of single stage magmatic hydrothermal mineralization or superposition of multi-stage mineralization remains unclear. Therefore, detailed geological and geochemical analyses of in-situ S isotopic compositions of sulfide and sulfate, trace elements of sphalerite, and ore Pb isotopic compositions were performed to decode the source and genesis of the Chapai deposit. Based on the investigation and microscopic observation, mineralization of the Chapai Zn–Pb deposit has obvious early hydrothermal alternation in the early hydrothermal sulfide stage (S1) and the late hydrothermal sulfide stage (S2) as well as the supergene oxidized mineralization stage (S3). The trace elements Cu, Ag, Ga, Sb, As and Ge are incorporated into S1 and S2 stages of sphalerite mainly through the following substitution mechanisms: Zn2+↔ (Fe2+, Cd2+),2Zn2+↔ (Ag+, Cu+) +(As3+, Ga3+, Sb3+), 3Zn2+↔ Ge4++2(Cu++Ag+), 4Zn2+↔(Cu++Ag+) + Sb3++Ge4++□(vacancy). In situ δ34S values of sulfides and sulfates are within a greater range (–3.0 to + 32.2 ‰), and are significantly higher in S2 compared to S1 stage, implying the mixing of two isotopically different end-members of hydrothermal fluids and wall rocks by sulfate reduction. The S isotope of sphalerite and galena crystallized in the early stage close to 0 ‰ may be controlled by magmatic-hydrothermal fluid source, while the increased S isotope in the late stage may be derived from the increased decomposition of organic matter and organic sulfate reduction (TSR). The Pb isotopic data (206Pb/204Pb = 18.355 ∼ 18.819, 207Pb/204Pb = 15.720 ∼ 15.778, and 208Pb/204Pb = 38.912 ∼ 39.222) indicate that the sources of metallogenic materials in the Chapai deposit are primarily upper crust basement rocks. The geothermometer studies of sphalerite in Chapai deposit show that it was generated from a medium–low temperature (142 ∼ 255 °C) condition. The low Zn/Cd ratios and high concentrations of Cd and Ge in sphalerite are in agreement with those of Mississippi Valley-type (MVT) deposits. Hence, the Chapai deposit was formed in a medium–low temperature magmatic- hydrothermal system and can be categorized as a MVT deposit within Nanling region (NR).