The Eastern Lake Region is the most eutrophic in China and is most affected by human activities. In recent years, phytoplankton have proliferated in most lakes in the lake region, with the frequent occurrence of water blooms, and the driving mechanisms and spatial differences for long-term changes in the phytoplankton community of lakes at the regional scale remain unclear. Among them, Lake Taihu, Lake Hongze, and Lake Luoma are located in the Yangtze River Economic Zone and have important ecological functions such as storage, drinking water, and irrigation. They are greatly affected by human activities and are typical lakes in the Eastern Lake Region. We used hydro-meteorological data, physical and chemical index data, and phytoplankton biomass data from 2016 to 2021 to study the phytoplankton community changes in typical lakes in the Eastern Lake Region based on redundancy analysis and combined hierarchical partitioning and variance decomposition to identify the main drivers of phytoplankton community changes. The results showed that the long-term trends of climate background were generally consistent among typical lakes in the Eastern Lake Region, but their nutrients, phytoplankton community, and environmental driving factors were different. The dominant phytoplankton phyla and genera in Lake Taihu, Lake Hongze, and Lake Luoma were significantly different. The lake characteristic, mainly characterized by water depth, was the main driving factor that led to spatial differences in phytoplankton communities among typical lakes in different seasons. The explanatory rates of water depth in spring, summer, autumn, and winter were 46.32%, 30.79%, 26.92%, and 35.80%, respectively. However, the secondary driving factors had seasonal differences. Among them, in spring, the secondary driving factors were conductivity （13.48%） and total nitrogen （12.74%）. In summer, the secondary driving factors were total phosphorus （19.02%） and conductivity （14.71%）. In autumn, the secondary driving factors were total phosphorus （19.43%） and dissolved total nitrogen （15.86%）. In winter, the secondary driving factors were total phosphorus （23.53%） and the daily minimum temperature （14.91%）. Quantifying the contribution of different drivers was important for future lake eutrophication management and policy formulation.