Abstract: The Nalenggele River Basin, as a core water resource area in the Qaidam Basin, contains downstream salt lake groups that are critical components of a world-class salt lake industry base. Understanding the hydrochemical characteristics and formation mechanisms of groundwater in this basin is significant not only for deciphering the hydrochemical evolution processes in arid inland river basins and supporting the rational development and utilization of regional water resources, but also for providing a typical case study of hydrochemical processes associated with strategic resource enrichment in arid salt lake systems. This study systematically collected groundwater samples from the mountainous areas to the terminal salt lakes within the basin. By comprehensively applying methods including hydrochemical parameter analysis, hydrochemical diagrams, descriptive statistics, ion ratio analysis, and the chloro-alkaline indices, we analyzed the spatial variation patterns and formation mechanisms of groundwater hydrochemical characteristics in the Nalenggele River Basin. The results indicate that the groundwater has a pH range of 5.72–9.23 and TDS values ranging from 123 to 113600 mg/L, with significant spatial variations in major/trace elements and hydrochemical controlling factors observed across different geomorphological units. From the mountainous area to the saline plain, groundwater gradually transitions from weakly alkaline to weakly acidic. Concentrations of TDS, Na⁺, and Cl^- increase, while concentrations of Ca²⁺, Mg²⁺, HCO₃^-, and SO₄^2- decrease. The hydrochemical type evolves from Cl·SO₄-Na type to Cl-Na type. Analysis of ionic end-members reveals significant differences along the groundwater flow path. In the early stages of groundwater formation, silicate weathering and dissolution are the dominant processes. As the flow path lengthens and evaporation intensifies, the dissolution of evaporite rocks becomes the predominant mechanism, leading to the formation of a Cl-Na dominated ionic assemblage, during which cation exchange gradually strengthens. Groundwater acts as a strategic enrichment carrier for Li⁺ and B³⁺. The enrichment of these elements is primarily controlled by multi-source coupled geological processes, including deep hydrothermal input, rock weathering, and evaporative concentration, which are key drivers for the mineralization in the downstream salt lakes. This study reveals the spatial heterogeneity of groundwater chemical characteristics along the geomorphic units in the Nalenggele River Basin, identifies the dominant mechanisms of ion end-member differentiation and the controlling effects of multi-source coupled geological processes on the enrichment of Li⁺ and B³⁺. It provides a direct basis for the zonal utilization of water resources and the enrichment of salt lake resources in arid inland river basins.