Tree-ring width standard chronologies were created from juniperus przewalskii Kom data collected in the Lancang River Headwaters region. Statistical analysis results showed high correlation (r = 0.69) between the composite tree-ring chronology and instrumental streamflow records at the Xiangda Hydrological Station during the annual September-August interval. Streamflow of the Zaqu River in the Lancang river source region was reconstructed for the past 419 years. The model was stable and revealed 14 extremely dry years and 6 extremely wet years. The results showed relatively low streamflow periods occurred during 602-1614, 1633-1656, 1684-1697, 1712-1722, 1735-1753, 1817-1829, 1847-1861, 1874-1884, 1946-1959, 1961-1977, and 1990-2000. Relatively high streamflow periods occurred during 1615-1630, 1657-1678, 1698-1711, 1754-1783, 1803-1813, 1830-1840, 1862-1873, 1892-1909, and 1932-1945. Comparison with tree-ring based streamflow reconstructions and chronologies from surrounding areas provided a high degree of confidence in our reconstruction. The empirical mode decomposition analysis suggests the existence of significant periods with intervals of 2-4, 5-9, 11-16, and 26-50 years. Regional comparison indicated that our reconstruction was associated with large-scale atmospheric-oceanic variability, such as the El Niño-Southern Oscillation (ENSO), Atlantic Multidecadal Oscillation (AMO) index, Pacific Decadal Oscillation (PDO) index, and East Asian monsoon variation. This research provides a useful foundation for water resource planning and management guidance in the Three-River Headwaters Region.