This study focuses on the chemical composition, and the factors controlling it, of the high mountain-rivers in the source region of the Yangtze River on the Tibetan Plateau. By comprehensive and systematic analysis, the chemical signatures, spatial variations of water quality, as well as the factors controlling them are studied. The value of the average total dissolved solids (TDS) is 778 mg/l, ranging from 117 to 5496 mg/l. In order of decreasing concentration, the main cations are Na try of the river water is controlled by lithogenic weathering processes. The Na-normalized ratio end-member diagram indicates that the weathering of silicates and carbonates is relatively significant, on the whole. There exists pronounced regional heterogeneity in the water chemistry and the factors affecting it. The northern rivers, including Chumaer He, Beilu He, and Ranchiqu, are mainly affected by evaporation and crystallization processes, while the southern rivers (Tuotuo He, Gaerqu, and Buqu) show effects from the weathering of carbonates and silicates.