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Remnants of cities and farmlands in China’s hyperarid Tarim Basin indicate that environmental conditions were significantly wetter two millennia ago in a region which is barren desert today. Historical documents and age data of organic remains show that the Loulan Kingdom flourished during the Han Dynasty (206 BCE–220 CE) but was abandoned between its end and 645 CE. Previous archaeological, geomorphological and geological studies suggest that deteriorating climate conditions led to the abandonment of the ancient desert cities. Based on analyses of lake sediments from Lop Nur in the eastern Tarim Basin and a review of published records, we show that the Loulan Kingdom decline resulted from a man-made environmental disaster comparable to the recent Aral Sea crisis rather than from changing climate. Lop Nur and other lakes within the Han Dynasty realm experienced rapidly declining water levels or even desiccation whilst lakes in adjacent regions recorded rising levels and relatively wet conditions during the time of the Loulan Kingdom decline. Water withdrawal for irrigation farming in the middle reaches of rivers likely caused water shortage downstream and eventually the widespread deterioration of desert oases a long time before man initiated the Aral Sea disaster in the 1960s.