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The Liangzhu culture in the Yangtze River Delta (YRD) was among the world’s most advanced Neolithic cultures. Archeological evidence suggests that the Liangzhu ancient city was abandoned, and the culture collapsed at ~4300 years ago. Here, we present speleothem records from southeastern China in conjunction with other paleoclimatic and archeological data to show that the Liangzhu culture collapsed within a short and anomalously wet period between 4345 ± 32 and 4324 ± 30 years ago, supporting the hypothesis that the city was abandoned after large-scale flooding and inundation. We further show that the demise of Neolithic cultures in the YRD occurred within an extended period of aridity that started at ~4000 ± 45 years ago. We suggest that the major hydroclimatic changes between 4300 and 3000 years ago may have resulted from an increasing frequency of the El Niño–Southern Oscillation in the context of weakened Northern Hemisphere summer insolation.