We investigated major ions, stable isotopes, and radiocarbon dates in a Quaternary aquifer in semi-arid northwestern China to gain insights into groundwater recharge and evolution. Most deep and shallow groundwater in the Helan Mountains was fresh, with total dissolved solids <1,000 mg L−1 and Cl− <250 mg L−1. The relationships of major ions with Cl− suggest strong dissolution of evaporites. However, dissolution of carbonates, albite weathering, and ion exchange are also the major groundwater process in Jilantai basin. The shallow desert groundwater is enriched in δ18O and intercepts the local meteoric water line at δ18O = −13.4 ‰, indicating that direct infiltration is a minor recharge source. The isotope compositions in intermediate confined aquifers resemble those of shallow unconfined groundwater, revealing that upward recharge from intermediate formations is a major source of shallow groundwater in the plains and desert. The estimated residence time of 10.0 kyr at one desert site, indicating that some replenishment of desert aquifers occurred in the late Pleistocene and early Holocene with a wetter and colder climate than at present.