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Understanding coastal flooding processes in response to centennial-scale sea-level rise is essential in preparing for the challenge of present-day global warming. Mid-Holocene sea-level rise induced widespread coastal flooding along the East China coast and precipitated the collapse of the Neolithic Liangzhu Culture, the earliest known prehistoric state in East Asia. This paper presents multi-proxy analyses of sedimentology, grain size, total organic carbon (TOC), and alkaline-earth metals extracted by acetic acid (HAc) of a dated sediment core, ZK07, collected from Liangzhu City, with the aim of revealing the detailed progression of coastal flooding phases and the response of prehistoric people at the end of the associated Liangzhu Culture. A three-step succession of coastal flooding processes between ca. 4.6–4.3 cal kyr BP, brought about by relative sea-level rise, is evident in core ZK07. Initially, an increase in the local water level in response to the first phase of sea-level rise is indicated by a gradual increase in TOC at ca. 4630 cal yr BP. Subsequently, at ca. 4520 cal yr BP, a second phase of increased local water-level, consistent with further sea-level rise and salinity intrusion, is suggested by higher Sr concentrations accompanied by a sharp increase in TOC. Thirdly, at ca. 4480–4315 cal yr BP, low TOC content, high - but strongly fluctuating - Sr and Ba concentrations and coarser sediment grain size are all indicative of coastal inundation caused by both storm surges and river flooding associated with typhoon events that correspond with a concurrent phase of accelerated sea-level rise. Considering the evidence of cultural deposits preserved at Liangzhu City, it appears that the Liangzhu people were forced to respond rapidly to the inundation by abandoning the city at ca. 4480 cal yr BP. We suggest that relative sea-level rise and coastal flooding at the terminal stage of the Liangzhu Culture was the regional response to global climate warming and eustatic sea-level rise at that time. Given evidence that a contemporaneous cultural transition took place in the lower Yellow River basin, we further propose that global climate change around 4.5 cal kyr BP had a widespread impact on Neolithic cultural evolution in East China. Furthermore, the rise in local water levels and associated salinity intrusions may be considered as an early warning signal in monitoring future coastal flooding risk. • A three-step succession of coastal flooding was recognized at the end of Liangzhu Culture. • Rise in local water level and salinity intrusion could be early warning of coastal flooding. • Global climate warming and eustatic sea-level rise at ca. 4.5 ka was the major mechanism. • Contrasting Neolithic cultural evolution occurred in the lower reaches of two large rivers in East China. [ABSTRACT FROM AUTHOR]