This paper takes the Chaohu Lake Basin as the study area, constructs a remote sensing ecological index (RSEI) based on Landsat TM/OLI series remote sensing data from 1999 to 2020 through the Google Earth Engine cloud computing platform, and uses spatial autocorrelation and geodetectors and other methods to conduct large-scale, long time-series dynamic monitoring and analysis of the ecological environmental quality of the Chaohu Lake Basin. The results show the following: (1) the mean value of the RSEI in the study area increased from 0.68 in 1999 to 0.72 in 2020, showing an overall improvement trend, and the ecological environment of the study area was mainly excellent and good. (2) The global Moran’s I index in the study area was greater than 0. The ecological environmental quality of the Chaohu Lake Basin showed a clustering trend in terms of global autocorrelation with significant positive spatial correlation, and the “high-high” clustering and “low-low” clustering characteristics were most obvious from 1999 to 2020. (3) The ecological environment in the study area has been influenced by multiple factors, among which human factors had a greater impact on the ecological environment of Chaohu Lake Basin in 2008, which led to a decline in ecological environment quality.