The streamflow of the Bailong River, which is a secondary tributary of the Yangtze River located on the eastern Tibetan Plateau, has declined in recent decades. Although instrumental records for the Bailong River are short, historical streamflow reconstructions enable us to evaluate the recent streamflow reductions from a multi-century perspective. Here, we present the first water-year streamflow reconstruction for the Bailong River using six tree-ring chronologies covering the period 1681–2017 CE. The reconstruction shows that the recent declines in streamflow are unprecedented over the past 337 years, with the most prolonged and severe low flows occurring in the 1990s and 2000s. Together, higher temperatures and declining precipitation have resulted in a decrease in the streamflow of the Bailong River. The mean contribution of temperature to streamflow departures is about −10.5%, while the mean contribution of precipitation to streamflow departures is about −4% for the period 1995–2011 CE. We find that temperature has a stronger influence on streamflow than precipitation, and that the influence of temperature on streamflow has increased since 1995. At the same time, the runoff efficiency has decreased dramatically. With regard to large-scale climatic forcing, ENSO and NAO exert a significant influence on the regional moisture and streamflow variations by regulating the water vapor flux and the Asian Monsoon. Extreme high-streamflow events correspond with the negative ENSO mode and the positive NAO phase. Continued warming will likely cause a continued decline in the streamflow of the Bailong River, with repercussions on the local water supply, societal well-being, and economic development.