Eastern Asia (EA) is a key region for the diversification of flowering plants in the Northern Hemisphere, but few studies have focused on the biogeographic history within EA in the context of the other northern continents. Polygonatum is an important medicinal genus widely distributed in the Northern Hemisphere with its highest species richness in EA, and it represents an excellent model for studying the evolution of biogeographic patterns in this region. Divergence time estimation was used to examine the biogeographic history of Polygonatum based on nuclear ITS and four plastid sequences (rbcL, matK, psbA–trnH and trnC–petN) from 30 Polygonatum species and 35 outgroup taxa. The ancestral area of Polygonatum and subsequent dispersal routes were inferred using Bayes-Lagrange. Polygonatum was estimated to have originated in southern EA during the middle Miocene (14.34–13.57 Ma) with subsequent south-to-north expansion in the late Miocene. Multiple intercontinental dispersal events were inferred between EA and Europe or North America, and all of them have occurred recently in the late Miocene to Pliocene. The separation of Polygonatum into the south and north lineages and their subsequent diversifications in the late Miocene supports the existence of a biogeographic divide between the northern and southern parts of EA that also coincides with the retreat and redevelopment of the arid zone in EA in the Neogene. Our results demonstrate the complexity of biogeographic history of Polygonatum in the Northern Hemisphere including early vicariance followed by frequent and recent dispersals in the Neogene.