Abstract: This study measured the spatial and temporal differentiation characteristics of land use transformation patterns and ecological environment quality in the “Yangtze River Delta” urban agglomeration from 1980 to 2020, using the methods of land use transfer matrix and ecological environment quality index. The remote sensing image data in 1980, 2000, and 2020 were used. Apart from that, the driving mechanism of the ecological environment quality in this region was explored by adopting geographic detector model. The results show that: (1) the “three lives” of the “Yangtze River Delta” urban agglomeration demonstrated a significant spatial differentiation from 1980 to 2020. Production and living land were concentrated in the Yangtze River Basin floodplain and the northeast coastal areas, with an overall decrease trend in production land and a rapid increase in living land in terms of an expanding trend. Ecological land mainly distributed in the hilly and mountainous areas of southern Anhui and northern Zhejiang and the floodplain zone. (2) The ecological environment quality of the “Yangtze River Delta” urban agglomeration experienced a “U-shaped” evolution process of decreasing and increasing over time, with the lowest quality in 2000. In general, a spatial distribution pattern of “high quality in the south and low quality in the north” was indicated. In particular, a low-quality area centered in Yancheng, Taizhou, Nantong, and Shanghai, a median-quality area in a belt shape in the Yangtze River Basin, and a high-quality area centered in Hangzhou of northern Zhejiang and southern Anhui. (3) Factors of land development intensity (X16), policy attention level (X17), fixed asset investment in society (X9), unit area grain yield (X10), urban green area (X15), carbon emissions (X13), and urbanization rate (X6) were the main ones influencing ecological environment quality in the “Yangtze River Delta” urban agglomeration.