Mining activities change the groundwater level and flow conditions through pumping and drainage, which enhances the interaction between groundwater and aquifer rocks; mine drainage is discharged into the surface water system, which affects the whole karst water hydrogeochemical process. Based on hydrogeochemistry and the δ34S isotope, the hydrogeochemical processes, characteristics, and main controlling factors for waste water, karst groundwater, and surface water in a typical Carlin gold mining area and its surrounding areas were revealed. The results showed that:chemical compositions of groundwater and surface water unaffected by gold mining activities were mainly controlled by the weathering of limestone and dolomitic limestone; Ca2+, Mg2+, and HCO3- were main ions; and the water chemical types were Ca-HCO3. The mine wastewater and its downstream receiving water were affected by the dissolution of carbonate and silicate minerals, and cation exchange also played a role; the main ions were Ca2+, Mg2+, Na+, and SO42-, and the hydrochemical type gradually evolved from Ca-HCO3 to Ca-SO4. SO42- was the characteristic component in various water bodies affected by mining, and the concentration of SO42- gradually decreased from top to bottom in the well. The values of δ34S for unaffected groundwater and surface water were positive, and SO42- was mainly derived from realgar oxidation. Conversely, mine wastewater and downstream water were negative, SO42- was mainly influenced by the mixing action of realgar oxidation and meteoric precipitation, and pyrite also contributed to a certain extent. At the same time, NO3- came from agricultural fertilizer and rural domestic sewage discharge directly. Principal component analysis (PCA) further demonstrated:sulfide mineral oxidation and mining activities were the main controlling factors for the water chemical composition of mine wastewater and downstream water, whereas unaffected groundwater and surface water were mainly influenced by water-rock (carbonate rock) interactions. Agricultural fertilizer and rural sewage discharge also had a certain influence. Therefore, the study area should strengthen the interception of surface water, control-block-management of sulfide oxidation, rural domestic sewage treatment, and agricultural fertilizer.