The chemical and stable isotopic compositions (δ³⁴S_SO4 and δ¹⁸O_SO4) 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 δ³⁴S_SO4 values ranging from −9.1 to 5.1‰ (mean value = −2.1‰) and δ¹⁸O_SO4 values ranging from −0.4 to 10.8‰ (mean value = 5.0‰). The δ³⁴S_SO4 and δ¹⁸O_SO4 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