In hyper-arid regions, groundwater serves as a critical nexus linking various components of the Earth system. However, due to the extensive sand mantle, the history and controlling factors of groundwater in these regions, as well as their relationship with global climate, remain poorly understood. To shed light on these issues, this study focuses on the Alxa Plateau sandy desert (mainly involving Badain Jaran Desert and Tengger Desert) in northern China and analyzes the soluble salts from two drill cores in the desert interior, and from modern dunes, lake waters, springs and dry lakebeds. Combined with regional hydrological, stratigraphic, and paleoenvironmental evidences, the history of groundwater activity in the desert was systematically reconstructed. The results revealed that two significant decreases of soluble salts in the desert strata occurred at 1000 and 500 ka, respectively, indicating stepwise enhancement of regional groundwater activity. In desert regions, aeolian sand layers function as critical aquifers, of which formation, structure, and evolution fundamentally govern groundwater dynamics. In the Alxa Plateau sandy desert, these aeolian sand layers first appeared similar to 1000 ka and further thickened after 500 ka, markedly enhancing the spatial mobility and diffusion of groundwater across the desert. Similar stratigraphic conversions also existed in other deserts across northern China. Global glacial-interglacial rhythms, in response to the Mid-Pleistocene Transition and the Mid-Brunhes Event, continuously regulated the production, deposition and deflation of aeolian sands, and regional humidity in the sand sea, which further determined the evolution of the desert stratigraphic architecture, finally leading to enhanced groundwater activity, accumulation of soluble salt on the surface, and soluble-salt-bearing dust releasement. This finding has significant implications for the assessment and exploration of groundwater resources in hyper-arid regions.