River systems have critical roles in the natural water environment and the transportation of nutrients. Anthropogenic activities, including wastewater discharge and river damming, raise adverse impacts on ecosystem and continuum of rivers. An increasing amount of attention has been paid to riverine bacterioplankton as they make vital contributions to biogeochemical nutrient cycle. A comprehensive study was conducted on the bacterioplankton community along the Yarlung Tsangpo River, which is the longest plateau river in China and is suffering from various anthropogenic impacts. The results indicated that nutrient variations corresponded to anthropogenic activities, and silica, nitrogen and phosphorus were retained by the dam. River damming influenced the biomass and diversity of the bacterioplankton, but significant alterations in the community structure were not observed between upstream and downstream of the dam. Moreover, the spatial distribution of the bacterioplankton community changed gradually along the river, and the dominant bacterioplankton in the upstream, midstream and downstream portions of the river were Firmicutes, Bacteroidetes and Proteobacteria, respectively. Soluble reactive phosphorus, elevation, ammonium nitrogen, velocity and turbidity were the main environmental factors that shape the bacterioplankton community. Our study offers the first insights into the variation of a bacterioplankton community of a large river in plateau region.