The Dunhuang Basin, located in northwestern China, is famous for its oases and geological remains. However, some problems of the eco-environment have raised public concern in recent decades. Land use/land cover change (LUCC) has been considered essential reference for studying eco-environment across the world. In the present study, the land use/land cover was divided into natural water, salt marshes, Aeluropus littoralis, natural vegetation, barren land, and desertified land. The LUCC was analyzed using four temporal Landsat images (from around 1975, 1990, 2000, 2010, respectively) and RapidEye images in 2010. Firstly, vegetation degeneration is the most serious problem, and 926.74 km2 turned into bare land in the past 35 years. The total area of bare land increased mainly occurred during 1975–1990. The area of desertified land increased rapidly from 2000 to 2010. Secondly, wetlands have experienced extreme shrinking; some areas degenerated into salt marshes, subsequently vanished. Salt marsh areas have been continually decreasing and gradually degenerating into saline and alkaline lands and bare land. In relation to the driving forces of LUCC, according to collected data and interpretation results by remote sensing images, the surface water environment is destructive due to three reservoirs impede surface water supplementation to the soil and natural vegetation. In addition, excessive pumping of groundwater occurred in the study area. Based on the local soil profiles of vadose zones and dynamic change of groundwater level, the groundwater flow system is another key factor, which developed along with the spatial distribution of groundwater recharge, runoff, and discharge conditions. Furthermore, large-scale activities connected to the reclamation of commercial farmlands have also promoted the LUCC.