The chemical and stable isotopic compositions (δ34SSO4 and δ18OSO4) of Xijiang River water in southwest China, were measured to determine the extent of rock weathering and associated CO2 consumption rates, and to assess the contamination sources of river water. The SO42− concentration in the river water was in the range of 0.05 to 0.96 mmol L−1 (mean value = 0.32 mmol L−1) and was characterized by δ34SSO4 values ranging from −9.1 to 5.1‰ (mean value = −2.1‰) and δ18OSO4 values ranging from −0.4 to 10.8‰ (mean value = 5.0‰). The δ34SSO4 and δ18OSO4 values ranged from high to low from the upper reaches to the lower reaches in all the river water samples. The results indicate that the oxidation of sulfide and anthropogenic inputs are the dominant processes affecting SO42− sources and S cycling of the Xijiang River during high‐discharge conditions, which are controlled by regional hydrological processes that are affected by natural processes and anthropogenic inputs Core Ideas: The dual isotopes (δ34SSO4 and δ18OSO4) of sulfate indicated S sources.The weathering rates of carbonate and silicate were calculated.The relative contributions of various sources are identified.