Some rivers on the northern slope of the eastern Kunlun Mountains in the Qaidam Basin, China, show very high concentrations of boron and lithium. Correspondingly, the salt lakes fed by these rivers show an unusual enrichment of boron and lithium, and become an important economic resource. The origin of boron and lithium has long been debated. The aim of this study is to analyze the water chemistry and hydrogen and oxygen isotopic composition of river water to understand the unusual enrichment of boron and lithium in the salt lakes of the Qaidam Basin. Oxygen and hydrogen isotope data show that the source of river water in the winter and summer originates from the Kunlun Mountain ice and snow melt water, respectively. The water chemistry shows that boron and lithium contents are high but little variable with seasons in the Nalenggele River and Wutumeiren River waters. By contrast, other rivers have much lower lithium and boron contents. Moreover, the contents of B3+ and Li+ in the river loads or bed sands show little difference amongst the rivers. This indicates that removal by adsorption or input by surface rock weathering is not the main controlling factor of the B3+ and Li+ variation in the rivers. Rivers with high B3+ and Li+ content are chemically similar to geothermal waters in the Tibetan Plateau. In addition, the source area of the Nalenggele River is located in a collision zone of the Kunlun Mountains and Altun Mountains. Large and deep faults can serve as conduits for geothermal fluids. Thus, deep geothermal waters in the source area can easily migrate to the surface and discharge as springs feeding the rivers. They are an important source of B3+ and Li+ to the rivers. The abnormally high contents of B3+ and Li+ in the Nalenggele and Wutumeiren Rivers also suggest that the geothermal source area may be a future target for boron and lithium resources.