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Climate change has influenced the glaciers and water resources in the Hindukush-Karakorum-Himalaya region. The relatively short instrumental record of northern Pakistan makes long-term climate change assessments difficult. In this paper, tree-ring width chronologies were developed from two stands of spruce species (Picea smithiana) in the Karakoram region of northern Pakistan. The results of the correlation analysis revealed that tree-ring growth of spruce was limited by annual (June-May) precipitation. Based on the regional chronology, we developed an annual precipitation reconstruction for the period 1540-2016 CE. The precipitation reconstruction equation accounts for 40% of the regional precipitation variance during the instrumental period 1946-2016. Dry episodes with rainfall below the 477-year average occurred from 1569 to 1577, 1598 to 1612, 1621 to 1621, 1638 to 1654, 1673 to 1680, 1697 to 1720, 1728 to 1739, 1753 to 1761, 1777 to 1793, 1801 to 1840, 1860 to 1874, 1914 to 1932, 1960 to 1985, 1998 to 2011. Wet episodes occurred from 1540 to 1568, 1578 to 1597, 1613 to 1620, 1632 to 1637, 1655 to 1672, 1681 to 1696, 1721 to 1727, 1740 to 1752, 1762 to 1776, 1794 to 1800, 1841 to 1859, 1875 to 1913, 1933 to 1959, 1986 to 1997. Furthermore, the results of spatial correlation analyses show that the reconstructed precipitation represents the regional precipitation variations for northern Pakistan and nearby high-altitude mountains. The out-of-phase relationship in tree-ring records of the Karakoram region and surrounding areas suggests that the Karakoram was under the control of large-scale ocean-atmosphere-land circulations on a decadal timescale in the past centuries. In addition, by the comparison between the precipitation reconstruction and the instrumental data, we found that the drought risk of Karakoram has increased in the past 70 years and that extreme events are likely to become more severe and more frequent under the backdrop of climatic warming.