The Weihe River Basin (WRB), the largest tributary of the Yellow River Basin (YRB), is located in the northwest of China. As the "mother river" of the Guanzhong Plain, it plays an important role in the development of Guanzhong City Group. Based on pH, electric conductivity (EC), total dissolved solids (TDS), and major ionic concentrations of 227 samples collected from the main stream (MS), northern tributaries (NT), and southern tributaries (ST) of the WRB, we explored spatial differential characteristics of hydrochemistry and their controlling factors, solute sources, and water quality of surface water. The results revealed mildly alkaline pH and much higher TDS values than the global average with mean values of 7.9 and 1037.7mgL-1, respectively. Except NO3-, the concentrations of major ions in the MS and NT were higher than those of the ST, with similar spatial distribution patterns of Ca2+, Na+, Mg2+, SO42-, and Cl-. Na+ and SO42- were the most dominant cation and anion in the MS and NT controlled by both rock weathering and evaporation-crystallization processes. Ca2+ and HCO3- were the most dominant cation and anion in the ST mainly controlled by rock weathering process. Evaporite dissolution contributed the most to dissolved solutes in the MS and NT, while carbonate weathering dominated dissolved solutes in the ST. These findings were confirmed by the results of correlation matrix, principal component analysis (PCA), stoichiometric plots, and different water types identified as Na-SO4·Cl in the MS and NT, and Ca-HCO3 in the ST. Atmospheric and anthropogenic inputs had a minor effect on the surface water chemistry. However, human activities could not be ignored in the ST accounting for 10.9% of the total dissolved solutes, mainly because of the fertilizer application. And the surface water of the ST was more suitable for irrigation and drinking purposes than that of the MS and NT. Knowledge of our findings could contribute new insights to the solute geochemistry and sustainable management of water resources in the lithologically distinct segments of the WRB and other similar areas.