Asian summer monsoon (ASM) variability and its long-term ecological and societal impacts extending back to Neolithic times are poorly understood due to a lack of high-resolution climate proxy data. Here, we present a precisely dated and well-calibrated treering stable isotope chronology from the Tibetan Plateau with 1- to 5-y resolution that reflects high- to low-frequency ASM variability from 4680 BCE to 2011 CE. Superimposed on a persistent drying trend since the mid-Holocene, a rapid decrease in moisture availability between similar to 2000 and similar to 1500 BCE caused a dry hydroclimatic regime from similar to 1675 to similar to 1185 BCE, with mean precipitation estimated at 42 +/- 4% and 5 +/- 2% lower than during themid-Holocene and the instrumental period, respectively. This second-millennium-BCE megadrought marks the mid-to late Holocene transition, during which regional forests declined and enhanced aeolian activity affected northern Chinese ecosystems. We argue that this abrupt aridification starting similar to 2000 BCE contributed to the shift of Neolithic cultures in northern China and likely triggered human migration and societal transformation.