As a potential source of arsenic (As) for the downstream region of the South and East Asia, the As contamination in the Qinghai-Tibet Plateau (QTP) still needs more investigation. In this study, As concentrations in the surface water, lake sediments, and fish of lakes and endorheic rivers in the central Tibet Plateau (CTP) were investigated for the better understanding of As fate in the CTP. Extremely high levels of As in saline lakes water were found with concentrations up to 10,775.40 mu g/L, while the lowest level of As was found in freshwater lakes with a concentration of only 1.80 mu g/L. Natural loading and evaporation concentration were the main reasons for As accumulation in saline lakes in the CTP. Rock weathering and terrestrial ecosystem could affect the As level in the lake. As contents in lake sediments significantly positive related to the As/EC ratios but showed no correlation with As concentrations in the water. Although As levels in the fish were higher in lakes with higher As concentrations, they were still lower than those of the fish from As-contaminated lakes in other studies. Results of this study indicate that hot spots of As in the CTP require more in-depth attention and studies in the future to better understand their influence on the fragile CTP aquatic ecosystem.