The 4.2 ka event has been widely investigated since it was suggested to be a possible cause for the collapse of ancient civilizations. With the growth of proxy records for decades, however, both its nature and its spatial pattern have become controversial. Here we examined multi-proxy data of the grain-size distribution, ostracode assemblage, pollen assemblage and the pollen-reconstructed mean annual precipitation from a sediment core at Hulun Lake in northeastern Inner Mongolia spanning the period between 5000 and 3000 cal yr BP to identify the nature and the associated mechanism of the 4.2 ka event occurring in the monsoonal region of eastern Asia. Higher sand fraction contents, littoral ostracodes abundances and Chenopodiaceae pollen percentages together with lower mean annual precipitations reveal a significant dry event at the interval of 4230–3820 cal yr BP that could be a regional manifestation of the 4.2 ka event in the northern margin of the East Asian summer monsoon (EASM). We suggest that the drought would be caused by a large decline in the intensity of the EASM on millennial-to-centennial scales that could be physically related to persistent cooling of surface waters in the western tropical Pacific and the North Atlantic. The cooling of western tropical Pacific surface waters could reduce moisture productions over the source area of the EASM, while the cooling of North Atlantic surface waters could suppress northward migrations of the EASM rainbelt, both leading to a weakened EASM and thus decreased rainfall in the northern margin of the EASM.