The Tarim River Basin is the largest inland river basin in China. It is located in an extremely arid region, where agriculture and animal husbandry are the main development industries. The recent rapid rise in population and land demand has intensified the competition for urban land use, making the water body ecosystem increasingly fragile. In light of these issues, it is important to comprehensively grasp regional land structure changes, improve the degree of land use, and reasonably allocate water resources to achieve the sustainable development of both the social economy and the ecological environment. This study uses the CA-Markov model, the PLUS model and the gray prediction model to simulate and validate land use/cover change (LUCC) in the Tarim River Basin, based on remote sensing data. The aim of this research is to discern the dynamic LUCC patterns and predict the evolution of future spatial and temporal patterns of land use. The study results show that grassland and barren land are currently the main land types in the Tarim River Basin. Furthermore, the significant expansion of cropland area and reduction in barren land area are the main characteristics of the changes during the study period (1992–2020), when about 1.60% of grassland and 1.36% of barren land converted to cropland. Over the next 10 years, we anticipate that land-use types in the basin will be dominated by changes in grassland and barren land, with an increasing trend in land area other than for cropland and barren land. Grassland will add 31,241.96 km2, mainly in the Dina River and the lower parts of the Weigan-Kuqu, Kashgar, Kriya, and Qarqan rivers, while barren land will decline 2.77%, with significant decreases in the middle and lower reaches of the Tarim River Basin. The findings of this study will provide a solid scientific basis for future land resource planning.