Abstract: Based on the remote sensing data in 1998, 2007, and 2016, the spatiotemporal changes of land use and landscape pattern as well as the driving forces in southern Gurbantunggut Desert in recent 19 years were analyzed from the aspects of land use structure, changing speed, and landscape patterns using ArcGIS and Fragstats software. The results showed that: (1) The proportion of sand land was the largest, but its dominance decreased. The proportion of farmland/grassland and construction land increased, while that of water area decreased. The decrease rate of other unused land was the largest. (2) At the level of landscape patch, the fragmentation degree of the sand land and other unused land increased, and the farmland/grassland area was enlarged with a more complicated and irregular shape. (3) At the overall level of landscape, the number and density of landscape patch increased, the shape was more irregular and complicated, the contagion decreased, and the degree of separation and dispersion increased. The landscape patches tended to discretely and discontinuously distribute. (4) The changes of landscape pattern were influenced by both natural and human factors, with human activities being dominant. Our results revealed that human activities had a great impact on the landscape pattern evolution in the southern margin of the Gurbantunggut Desert, which has an important guiding significance for the protection and restoration of desert vegetation in the future.