To understand the current eutrophication status, main drivers of eutrophication and restoration strategy of Yangtze-connected or Yangtze-isolated lakes (historically connected to the Yangtze River but isolated by artificial dikes currently), the trophic parameters and main water quality variables were surveyed seasonally in 27 large lakes and reservoirs of this region during 2017 to 2018. In addition, the temporal eutrophication dynamics and associated driving mechanisms of these lakes over the past 30 years were analyzed based on the historical data of these lakes (investigated during 1988 to 1992 and 2008). Our results showed that most of the lakes in the middle and lower reaches of Yangtze River were eutrophic now, and significantly worse than the status of 1988 to 1992, mainly contributed by chlorophyll-a of phytoplankton and total phosphorus. Human activities, including changes of water retention time (primarily depend on the lake-Yangtze connection condition), fishery activities, catchment pollution condition, and lake restoration are decisive factors in shaping the eutrophication status of these lakes. Comparing with the historical records, phytoplankton chlorophyll-a and associated organic matter concentrations are increased drastically, while nutrients (e.g., total phosphorus and nitrogen) experienced relatively small increase, yet. Therefore, it is suggested that the non-nutrients factors were the major causes which strengthen the eutrophication risk. From the perspective of restoration strategies of lakes in the middle and lower reaches of Yangtze River, it is crucial that rebuild the hydrological connectivity, restore natural water level fluctuation, optimize the fishery management and enhance the catchment nutrient abatement ability and applying the in-lake restoration engineering.