The 4.2 ka event is widely presumed to be a globally widespread aridity event and has been linked to several episodes of societal changes across the globe. Whether this climate event impacted the cultural development in south-central China remains uncertain due to a lack of regional paleorainfall records. We present here stalagmite stable carbon isotope and trace element–based reconstruction of hydroclimatic conditions from south-central China. Our data reveal a sub–millennial scale (~5.6 to 4.3 ka) drying trend in the region followed by a gradual transition to wetter conditions during the 4.2 ka event (4.3–3.9 ka). Together with the existing archaeological evidence, our data suggest that the drier climate before 4.3 ka may have promoted the Shijiahe culture, while the pluvial conditions during the 4.2 ka event may have adversely affected its settlements in low-lying areas. While military conflicts with the Wangwan III culture may have accelerated the collapse of Shijiahe culture, we suggest that the joint effects of climate and the region's topography also played important causal roles in its demise.