ABSTRACT Accurate analysis of regional eco-environment quality (EEQ) changes is essential for urban sustainability. Most of the widely used EEQ indicators ignore the impact of air pollution caused by urbanization and economic growth. This study proposed a remote sensing-based approach using a time-series comprehensive evaluation index (CEI), which was developed by PM2.5 concentration, Land surface temperature (LST), and vegetation coverage (VC) to assess the EEQ in the Demonstration Zone of Green and Integrated Ecological Development of The Yangtze River Delta (demonstration zone) from 2000 to 2020. The EEQ changes of all districts and townships were classified into five levels. The results suggested that from 2000 to 2020, the CEI was significantly decreased (p < 0.01) in the demonstration zone, indicating an overall improvement of the EEQ. Differences in the mean annual CEI values and EEQ changes were found among districts and to wnships. Higher CEI values, which indicated a lower degree of EEQ were found in areas where build-up land comprised a higher percentage of the total area. Townships with degraded EEQ change exhibited a higher percentage of increase in build-up land (32.3%) than others (8.67% to 16.68%) from 2000 to 2020. Moreover, the change of annual CEI at the administrative district scale was found to be strongly correlated with the proportion of the secondary sector in GDP in three districts. The results of our study indicated the importance of land use optimization, air pollution reduction, and vegetation coverage enhancement to improve the regional EEQ in the urban wetland ecosystems with rapid urbanization.