The semi-arid Hetao Plain in the northwest is one of the largest and earliest irrigated areas in the Yellow River Basin. The Hetao Plain has become the focus of attention due to its rapidly growing population and water requirements. In this study, the hydrographic geochemistry of surface water and groundwater in the Hetao Plain was researched, and the effects of geochemical processes and human activities on these characteristics were also investigated. Most water samples were hard-brackish or hard-fresh. The sodium absorption ratio indicated that most of the water was of moderate quality for irrigation, and the poor-quality water had greater Na+ concentrations. Three major water types were identified: Na-HCO3, Ca-Na-HCO3 and Na-SO4-Cl, and the predominance was Ca-Na-HCO3 which accounted for 55.3% of the water types. Geochemical and stable isotope data suggested that the releasing of principal solutes in the waters was mostly dominated by silicate weathering and dissolution, and the processes of cation exchange and evaporation also performed significant roles, and surface waters were influenced by evaporation and groundwater discharge. Correlation and principal component analyses indicated that pH, EC, TDS, Na, K, Mg, HCO3, SO4, Cl, delta 18O and delta D, with a correlation coefficient of no less than 0.37, are primarily affected by natural processes. Ca and Mg may be associated with the parent material of soil formation in the area. NO3 and PO4 are mainly dominated by anthropogenic impacts, and the use of chemical fertilizers, industrial wastewater and urban domestic sewage emissions had a significant influence on water chemistry.