The Sb source and the formation process of high Sb-contaminated mine water have not been well investigated. In this study, 11 mine water samples, 2 rainwater samples, 4 surface water samples, 4 D₃x⁴ (MA) water samples, and 4 D₃s⁴ (SA) water samples were collected from the largest antinomy mine in China. The δ³⁴S, δ¹⁸O, and δ²H data and the water-rock interactions were analyzed to reveal the source of Sb and geochemical behaviors of the mine drainage water. The Sb concentrations in mine water samples are 238-2420 times higher than the maximum acceptable Sb concentration (0.005 mg/L), according to China’s national drinking water quality standards. The chemical composition of the mine water is Ca-Na-SO₄, and the SA water is the main source of the mine water. It is also revealed that the Sb pollutant in the mine water is derived from the oxidation of stibnite. Moreover, the soluble oxygen in the mine water and the ion-exchange interaction between the mine water and surrounding rocks also contribute to the formation of high Sb-contaminated mine water. This study provides valuable information for Sb pollutant source control and water body protection in a mine area.