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Desertification is one of the main ecological environmental problems in Central Asia. To prevent and eradicate this problem, it is extremely urgent to monitor the long-term desertification process and assess the relative roles of its drivers. Based on an analytical hierarchy process, in this research, the spatiotemporal features of the desertification process were surveyed from 1982 to 2012 using four indicators. Further analysis was focused on determining the relative importance of multiple driving factors causing desertification in different ecosystems. The results revealed significant desertification expansion in the western part of Central Asia, with the most severe desertification occurring in eastern Xinjiang Province and the Ustyurt Plateau, with mean desertification indexes (DIs) as high as 0.8. According to a change-year analysis, mutation years of desertification were observed from 1993 to 2002 for most vegetation types. The desertification process for different vegetation types results from different major driving factors. Climatic factors, including decreased precipitation, increased temperature and drought, were the main drivers of desertification, especially for grasslands, forests and sparse vegetation. The desertification process of sparse vegetation and croplands was expanded and triggered by human activities: oil and gas exploration in the southern Ustyurt Plateau and agricultural abandonment in northern Kazakhstan. The results also indicated that after the collapse of the Soviet Union, rangeland abandonment in eastern Kazakhstan triggered desertification reversion in grasslands. Furthermore, due to inefficient irrigation water use, severe salt accumulation in croplands of the Amu Darya River delta resulted in desertification expansion in this region. In Central Asia, the desertification process in forests and areas of sparse vegetation was extremely sensitive to climatic variations, while that in croplands and grasslands was vulnerable to human activities. Therefore, regional governments should strive to reverse desertification to protect and improve this fragile, arid ecological environment.