Although the enrichment of arsenic (As) and boron (B) has been extensively observed in the major river basin within the Tibetan Plateau, little is known about the hydrogeochemical processes regulating the enrichment and mobility of As and B within river sediments. The present study conducted geochemical investigations of river sediments along the river flow path of the Singe Tsangpo River (STR) basin, and examined the mobility of As and B within river sediments under various environmental conditions through incubation experiments. The results suggested that the weathering of Cs-bearing silicate minerals could be a potential origin for As in the river sediments, which was evidenced by the corresponding variations between Cs and As (R = 0.60, P < 0.01). In contrast, carbonate weathering has contributed to the B enrichment, supported by the correlation between CaO and B concentrations (R = 0.60, P < 0.01). The incubation experiments showed intense mobilizations of As and B (∼12 mg/kg) under varying environmental conditions, where the increases in HCO 3 − concentration and temperature could enhance both As and B mobilization. Additionally, the As mobilization was enhanced by the anaerobic and alkaline conditions. These scenarios are relevant to the hydrogeochemical processes that regulate the As and B enrichment in both river water and groundwater from the STR basin, including the redox fluctuations that resulted from flood and draught cycling and the variations in the water/sediment particle ratios. The present study thus provided new insights into the hydrogeochemical control on the enrichment and mobility of As and B in the river sediments from the STR basin, which is also applicable in other riverine systems under similar conditions. • Geochemical characteristics in river sediments indicate different origins between As and B. • Geothermal water discharge contributes to As and B enrichment in river sediments. • Hydrologic disturbances could potentially regulate sediment As and B mobility.