Tree-ring width standard chronologies were created from Juniperus przewalskii Kom data collected in the southern Three-River Headwaters (TRH) region. Statistical analysis results showed high correlation between the first primary component (PC1) of the four chronologies and instrumental precipitation records during the annual September–August interval. Precipitation of the region was reconstructed for the past 461 years. It was verified that the reconstruction model was stable by split-sample calibration-verification statistics. The reconstruction series revealed 22 extremely dry years and 9 extremely wet years. Results showed relatively dry periods occurred during 1567–1597, 1604–1614, 1641–1656, 1684–1700, 1734–1755, 1817–1830, 1913–1932, 1953–1971, 1990–2005. Relatively wet periods occurred during 1615–1630, 1657–1683, 1701–1733, 1756–1786, 1798–1816, 1844–1855, 1864–1875, 1885–1912, 1933–1952, 1977–1989. Comparison with tree-ring based precipitation reconstructions, and chronologies from surrounding areas provided a high degree of confidence in our reconstruction, and correlated well with the Monsoon Asia Drought Atlas (MADA) dataset in the public section of corresponding grids. The empirical mode decomposition analysis suggests the existence of significant periods with intervals of 2–5, 6–10, 11–18, and 28–60 years. This research contributes to a better understanding of historical variations in precipitation and will aid in future plans to address climate change of the TRH region.