The vast drylands of the Asian interior were an integral part of a transcontinental network connecting east to west, that acted periodically as corridors and routeways for human migration. However, our understanding of the prehistoric human occupation of and interaction with this inhospitable environment has been hindered by a lack of direct evidence from settlements. Here we present the results of the first systematic study of archaeological material and radiocarbon dates from newly-discovered Bronze Age settlements in the hyper-arid Lop Nur region, in the eastern Tarim Basin. The studied settlement (the North Loulan Settlement, NLS), apparently associated with the prehistoric Xiaohe Culture, which is known from the Xiaohe and Gumugou cemeteries, is especially significant for the study of the prehistoric desert-oasis civilization in the drylands of the Asian interior, because it is quite different from any of the contemporary cultures in the surrounding regions. Based on a synthesis of Bayesian-modeled radiocarbon dates, the age of the NLS falls within the range of ca. 2051–1774 BC. Our field investigations indicate that the inhabitants of the site occupied semi-subterranean/semi-cave dwellings on the upper part of high yardangs, suggesting that they were able to utilize island-like yardangs in order to adapt to lake or wetland terrains. The new chronological framework for the Xiaohe cultural sites indicates that the NLS was the first Xiaohe settlement in the Tarim Basin. The earliest settlers, who were influenced by oriental culture, may have migrated to the NLS along the eastern or northeastern corridors. Later, there was the migration of populations westward along rivers.