Lake eutrophication has become a critical environmental issue due to the global effects of anthropogenic activities and climate change, and has been comprehensively studied for many years. A series of models and indicators have been proposed to assess the trophic state of lakes. The trophic state index (TSI) is a synthetic index that integrates chlorophyll-a, water clarity, and total phosphorus and is widely used to evaluate the trophic state of aquatic environments. In this study, we collected in situ lake samples (N = 431) from typical lakes to match Sentinel-2 MultiSpectral Instrument (MSI) imagery data using the Case 2 Regional Coast Color processor. Then we developed a new empirical model, TSI = -34.04 x (band 4/band 5) - 1.114 x (band 1/band 4) + 97.376). This model is valid for all of China, with good performance and few errors (RMSE = 7.36; MAE = 6.25) for the validation dataset. Recognizing that over 94% of the Chinese population located along eastern watersheds and large lakes have competing water uses, and given the TSI model on the seasonal scales, we further estimated the mean TSI and trophic state in eastern Chinese lakes (> 100 km(2)) from 2019 to 2020. The results revealed that more lakes were eutrophic in autumn (94.28%) than in spring (> 77.14%), indicating a serious eutrophication of eastern lakes. Although the eastern lakes have been studied in more detail, this study found that eutrophication still has markedly negative impacts on lake ecosystems. In addition, no significant improvement was observed in spring, most likely due to the months of curfew/lockdown from January 2020 onwards due to COVID-19. This may be due to the enrichment of nutrients deposited in sediment or watershed soil, which can be characterized as "autochthonous sources " of lake eutrophication, over decades with high rates of economic development. This study demonstrates the applicability of Sentinel-2 MSI data to monitor lake eutrophication as well as the feasibility of blue/red and red/red edge combinations. The framework and TSI model used bands available on MSI sensors to develop a novel approach for generating historical eutrophication data for large-scale evaluation of and decision-making related aquatic environmental changes, even in poorly studied areas.