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The Yangtze River Delta (YRD) is one of the regions with the most intensive human activities. The eutrophication of lakes in this area is becoming increasingly serious with consequent negative impacts on the water supply of the surrounding cities. But the spatial-temporal characteristics and driving factors of the trophic state of the lake in this region are still not clearly addressed. In this study, a semi-analytical algorithm for estimating the trophic index (TSI) using particle absorption at 645 nm based on MODIS images is proposed to monitor and evaluate the trophic state of 41 large lakes (larger than 10 km2) in the YRD from 2002 to 2020. The performance of the proposed algorithm is evaluated using an independent dataset. Results showed that the root-mean-square error (RMSE) of the algorithm is less than 6 and the mean absolute percentage error (MAPE) does not exceed 8%, indicating that it can be applied for remotely deriving the TSI in the YRD. The spatial-temporal patterns revealed that there were significantly more lakes with moderate eutrophication in the Lower Yangtze River (LYR) than in the Lower Huaihe River (LHR). The overall average value of the TSI reaches a maximum in summer and a minimum in winter. The TSI value in the YRD over the period 2002–2020 showed a downward trend, especially after 2013. Individually, 33 lakes showed a downward trend and 8 lakes showed an upward trend. Furthermore, marked seasonal and interannual temporal variations can be clearly observed in the LYR and LHR and the sum of the variance contributions of seasonal and interannual components is more than 50%. Multiple linear regression analysis showed that human activities can explain 65% of the variation in the lake TSI in the YRD. [ABSTRACT FROM AUTHOR]