The Yongding River basin is an important water conservation and ecological barrier area in the Northwest of Hebei Province. Reduced runoff and deterioration of the water environment in this area have become increasingly prominent under the effects of climate change and intensive human activities. Clarifying the chemical characteristics and factors of surface water and groundwater in the upper Yongding River basin can provide data and support for the sustainable use of water resources. Stable isotopes of hydrogen and oxygen (δ2H and δ18O) were used to study the sources of surface water and groundwater. Mathematical statistics and hydrogeochemical methods were then used to analyze the regional hydrogeochemical processes and factors of surface water and groundwater. The results showed that precipitation was the main source of surface water and groundwater. Under the effects of natural factors and human activities, the Yang River and Sanggan River basins exhibited significant differences in surface water chemistry. The sub-basins were ranked by ion concentration as follows: Sanggan River>Yang River. The main cation and anions of the Sanggan River basin were Na+, Cl-, and SO42-, while in the Yang River basin, Ca2+ and HCO3- were the most common. The water chemistry of the Sanggan River exhibited greater variation than that of the Yang River. Surface water chemistry were mainly controlled by mineral dissolution and evaporation, but human activities were reflected in different sub-basins. Surface water in the Sanggan River basin was affected by industrial wastewater discharge, while that of the Yang River basin was affected by agricultural production and cities. However, the continuous increase of Cl- and SO42- concentrations, caused by industrial wastewater discharge and acid rain, was the limiting factor for sustainable use of surface water resources. In future, surface water in Sanggan River basin should be used with consideration to the effects of both total salinity and chemical composition of the water, while in Yang River, a focus should be placed on total salinity. The use of surface water resources in accordance with local conditions is an effective measure for the sustainable use of water resources and the restoration of groundwater levels in this region.