This paper is the result of hydrogeological survey engineering. Objective Land Use/Cover Change (LUCC) caused by human activities is a critical part of global environmental change. LUCC in arid regions has a particularly significant impact on regional hydrology and ecology. Therefore, exploring LUCC and its response to human activities is of great significance to the sustainable development of ecology, resources and environment in the arid inland of Northwest China. Methods Based on the Landsat images during 1980 to 2018, this paper analyzes the characteristics of land use change in nine divisions of water resources of Tarim River Basin, by the combination of land use dynamic degree, land use transfer matrix and human activity intensity degree. Results In the past 40 years, cropland, constructive land and forest increased by 1.58×10⁴ km², 1.2×10³ km² and 347 km², respectively. By comparison, grassland, unutilized land, water and wetland decreased by 1.33×10⁴ km², 0.32×10⁴ km² and 815 km², respectively. The main stream of Tarim River Basin has experienced the most significant change in land use types among nine divisions of water resources, followed by Weigan, Aksu and Kashgar river basin. Since 2000, the equivalent area of constructive land and human activity intensity in Tarim River Basin has increased relatively fast, especially from 2000 to 2010. Conclusions Human activity intensity has showed significant spatial difference among division of water resources. Socio-economic development and policy guidance are major factors leading to land use change and human activity intensity difference.