We report dozens of direct radiocarbon dates on charred grains from 22 archaeological sites of the Neolithic and Bronze Ages in the Hexi Corridor, northwest China, a key region for trans-Eurasian exchange in prehistoric and historical times. These charred grains include remains of wheat and barley domesticated in southwest Asia and broomcorn and foxtail millet which originated from north China. Together with previously published radiocarbon dates, we consider these newly obtained radiocarbon results in the context of material cultures associated with them, to explore an episode of trans-continental cultural exchange foci at the Hexi Corridor. Our results show that millet cultivators who used painted potteries from the western Loess Plateau first settled the Hexi Corridor around 4800 BP. Communities who cultivated wheat and barley moved into this region from the west around 4000 BP, bringing with them technologies and materials not seen in central China before, including bronze metallurgy, mud bricks, and mace heads. This was part of the east–west contact which became evident in the Hexi Corridor since the late fifth millennium BP, and continued over the subsequent two millennia, and predated the formation of the overland Silk Road in the Han Dynasty (202 BC–AD 220).