We selected Tai Lake in China as the research area, and based on the Eco-lab model, we parameterized seven main external input conditions: discharge, carbon, nitrogen, phosphorus, wind speed, elevation, and temperature. We combined the LHS uncertainty analysis method and the Morris sensitivity analysis method to study the relationship between water quality and input conditions. The results showed that (1) the external input conditions had an uncertain impact on water quality. Among them, the uncertainties in total nitrogen concentration (TN) and total phosphorus concentration (TP) were mainly reflected in the lake entrance area, and the uncertainties of chlorophyll-a (Chl-a) and dissolved oxygen (DO) were mainly reflected in the lake center area. (2) The external input conditions had different sensitivities to different water layers. The bottom layer was most clearly and stably affected by input conditions. The TN and TP of the three different water layers were closely related to the flux into the lake, with average sensitivities of 83% and 78%, respectively. DO was mainly related to temperature and water elevation, with the bottom layer affected by temperatures as high as 98%. Chl-a was affected by all input factors except nitrogen and was most affected by wind speed, with an average of about 34%. Therefore, the accuracy of external input conditions can be effectively improved according to specific goals, reducing the uncertainty impact of the external input conditions of the model, and the model can provide a scientific reference for the determination of the mid- to long-term governance plan for Tai Lake in the future.