The Ulan Mulun River Basin is an essential ecological protective screen of the Mu Us Desert and a necessary energy base in Ordos City. With the acceleration of industrialization and urbanization, human activities have caused enormous challenges to the local ecological environment. To achieve the region’s economic sustainability and make local development plans more objective, it is necessary to evaluate the basin’s ecological environment quality over a period of time. First, in the Landsat historical images, we selected 5 years of data to investigate the changes in this time-period (2000–2020). Second, based on the opened remote sensing database on Google Earth Engine, we calculated the remote-sensing ecological index (RSEI) distribution map. RSEI includes greenness, temperature, humidity, and dryness. Thirdly, we assessed the ecological-environmental distribution and change characteristics in the Ulan Mulun River Basin. Finally, we analyzed the RSEI spatial auto-correlation distribution characteristics in the study area. The mean values of RSEI in 2000, 2005, 2010, 2015, and 2020 were 0.418, 0.421, 0.443, 0.456, and 0.507, respectively, which indicated that the ecological environment quality had gradually improved. The ecological environment quality from 2000 to 2005 had the biggest change, as the area with drastically changed water levels accounted for 78.98% of the total basin. It showed a downward trend in the central and western regions. It showed an upward trend in the eastern region. For 20 years, the area of deterioration decreased by 24.37%, and the slight change area increased by 45.84%. The Global Moran’s I value ranged from 0.324 to 0.568. The results demonstrated that the Ulan Mulun River Basin ecological environment quality spatial distribution was positively correlated, and the clustering degree decreased gradually. Local spatial auto-correlation of RSEI showed that high-high(H-H) was mainly distributed in the basin’s eastern and southern regions, where the population density was low and the vegetation was in good condition. Low-low(L-L) was mainly distributed in the basin’s central regions and western regions, where the population density was high, and the industrial and mining enterprises were concentrated. This study provided a theoretical basis for the sustainable development of the Ulan Mulun River Basin, which is crucial for the local ecological environment and economic development.