The water level of Poyang Lake is affected by both the Yangtze River mainstream and the Fiver Rivers (namely, Ganjiang River, Fuhe River, Xinjiang River, Raohe River and Xiushui River) in the lake basin. The runoff of the Five Rivers is the main inflow of Poyang Lake. In order to explore the temporal and spatial impact of the Five Rivers on the water level of Poyang Lake, the response of Poyang Lake level variation to the runoff change of the Five Rivers was quantitatively studied by data-driven simulation and sensitivity analysis. Firstly, the lake level prediction model was established by combining PSO-GA algorithm and support vector regression (SVR) technology. The temporal sensitivity of water level of Poyang Lake to runoff change of the Five Rivers was simulated. Then, based on this model, the spatial distribution characteristics of water level response of Poyang Lake to runoff change of the Five Rivers were studied using continuous model simulation. The results show that the most sensitive period that Poyang Lake level response to the runoff change of the Five Rivers is from May to July, especially in May. In terms of spatial distribution, water level in the middle part of Poyang Lake is most sensitive to the runoff change of the Five Rivers. For instance, based on the data in May 2010, when the runoff of the Five Rivers was increased by 40%, water level at Duchang station was averagely increased by 1.16 m within one week; Average water level increased at Xingzi station and Hukou station in the north lake area was 1.15 m and 1.03 m, respectively, and that at both Tangyin station and Kangshan station in the south lake area was 0.97 m. This study clarified the temporal and spatial response characteristics of water level of Poyang Lake to runoff of the Five Rivers, and provides scientific basis for water resources management and water projects optimization in the Poyang Lake basin.