The natural process of lake trophic status is controlled by both climatic-hydrological factors and ecosystem interactions. In order to recognize the response mechanism of lake nutrients to the multiple factors, 2 models were designed to simulate the lake nutrient changes over 16401840 A.D. in some lakes in the Yangtze floodplain. One was an exogenous-forced model with external driving forces from climate and catchment hydrological changes; the other was an endogenous-forced model with internal driving forces from the biological interactions within the lake ecosystem. After approval test and calibration, the simulation results by the 2 models had significant positive relationships with the observational records in 90th percentile, indicating robust simulation on the historical nutrient changes in 16401840 A.D. Results showed that (1) the simulated total phosphorus series by the combined exogenous-and endogenous-forced model were consistent with the reconstructed total phosphorus series from sediment cores in the 7 lakes in the Yangtze floodplain; (2) climate change was the primary factor for the long-term lake nutrient changes, whereas the feedback effects from lake ecosystem accounted for 40% of the nutrient changes; (3) the long-term changes of lake nutrients were significantly related with precipitation with 60% of the historical nutrient changes in synchronous response to precipitation changes. In addition, the responses of TP variations in the lakes smaller than 400 km~2 were more sensitive to climate changes than that in the large lakes over 2000 km~2.