A sound understanding of groundwater recharged from various sources occurring at different time scales is crucial for water management in arid and semi-arid river basins. Groundwater recharge sources and their geochemical evolution are investigated for the Heihe River Basin (HRB) in northwest China on the basis of a comprehensive compilation of geochemical and isotopic data. Geochemical mass-balance modeling indicates that mountain-block recharge accounts for a small fraction (generally less than 5%) of the shallow and deep groundwater sustaining the oasis, whereas infiltration of rivers and irrigation water contribute most of the groundwater recharge. Dedolomitization is the primary process responsible for the changes in groundwater chemical and carbon isotope compositions from the piedmont to the groundwater discharge zone, where the dedolomitization is very likely enhanced by modern agricultural activities affecting the shallow groundwater quality. Analysis of radioactive isotopes suggests that these primary recharge sources occur at two different time scales. Radiocarbon-derived groundwater age profiles indicate a recharge rate of approximately 12 mm/year, which probably occurred during 2000–7000 years B.P., corresponding to the mid-Holocene humid period. The recharge of young groundwater on the tritium-dated time scale is much higher, about 360 mm/year in the oasis region. Infiltration from irrigation canals and irrigation return flow are the primary contributors to the increased young groundwater recharge. This study suggests that groundwater chemistry in the HRB has been influenced by the complex interaction between natural and human-induced geochemical processes and that anthropogenic effects have played a more significant role in terms of both groundwater quantity and quality.