This research investigated anthropogenic inputs and chemical weathering in the upper reaches of the Datong River Basin, a tributary of the upper Yellow River, NW China. Multiple approaches were applied to data from 52 water and 12 soil samples from the Muli, Jiangcang, and Mole basins to estimate the chemical component concentrations and to analyze hydrochemical characteristics, distribution patterns, and origins in this coal mining-affected river basin. Coal mining has enhanced the weathering of the lithosphere in the study region. The total dissolved solids in the river range from 145.4 to 701.9 mg/L, which is higher than the global average for rivers. Ion concentration spatial distributions increase around mining areas. River geochemistry is mainly controlled by coal mining activity, carbonate weathering, and silicate weathering, with variances of 33.4%, 26.2%, and 21.3%, respectively. Ca2+, Mg2+, and HCO3? are mainly due to the dissolution of carbonate minerals (calcite > dolomite); Si and K+ are mainly from potassium (sodium) feldspar weathering; and Na+ and SO42? mainly from coal mine production. A conceptual model of the river water ion origins from the study area is presented and management implications for improving the adverse effects of coal mining are proposed. These results provide an important standard reference for water resource and environmental management in the study region.