In order to understand the characteristics and dynamic changes of the eco-climate in the Yangtze River Delta (YRD) urban agglomeration, based on the daily observation data of air temperature, precipitation, relative humidity and wind speed from 111 meteorological stations in the region, as well as the MODIS normalized difference vegetation index (NDVI) and land surface temperature (LST) data, remote sensing, GIS and principal component analysis (PCA) methods were used, and the existing remote sensing ecological index (RSEI) was improved. A regional integrated eco-climatic index (IECI) model was constructed from the aspects of dryness/wetness, comfortableness, greenness, heat and air cleanliness, and the dynamic change characteristics of the eco-climate in YRD urban agglomeration were analyzed. The results showed that during the period from 2001 to 2018, the fractional vegetation cover (FVC) of the urban agglomeration increased significantly with a linear trend of 2.80% per decade, the mixed layer height (MLH) decreased significantly at a rate of 51.3 m per decade, and the regional IECI decreased significantly with a linear trend of 0.10 per decade, showing a regional overall decreasing trend. Human activities and urbanization have significant effects on eco-climate change in the YRD urban agglomeration. It is necessary to strengthen the protection and improvement of eco-climate while promoting economic and social development, so as to achieve harmonious coexistence between humans and nature.