Lake Hongze is one of the most important lakes in the Huaihe River water system and the fourth largest freshwater lake in China. It plays an important role in flood control, irrigation, navigation, inter-basin water transfer, water resources and water environment protection. During the past 300 years, the surface area of Lake Hongze has undergone drastic changes due to the changing relationship between Yellow River and Huai River and the influence of human activities. The study on the spatial change of lake water area is helpful to understand the impact of basin environmental change and human activities. Based on ancient maps, historical documents and 7 phase remote sensing image datas from 1981-2016 since the early 18th century, we analyzed the spatial-temporal evolution of Lake Hongze over the past 300 years and its driving factors by using a combination of remote sensing and geographic information system technology in this paper. The results showed that over the past 300 years, the water area of Lake Hongze has presented a decreasing trend, with an interannual reduction rate of 0.17%. The lake area showed a shrinking trend from the surrounding to the center, and the most significant change was occurred in the southwest lake area. Specifically, before the middle of Qing Dynasty, the Yellow River rushed in Sishui and Huaihe River many times, and the change of Lake Hongze area was affected by relationship between the Yellow River and the Huaihe River, the construction of Gaojiayan and other water conservancy projects, and precipitation. By the end of the Qing Dynasty, the area of Lake Hongze decreased 743.05 km² from 3078.78 km² to 2335.73 km², and its spatial form also changed dramatically. During this period, the channel diversion of the Yellow River, precipitation and lakeside reclamation caused by population growth were the main reasons for the evolution of Lake Hongze. During 1949-2016, the area of Lake Hongze has been further reduced 269.17 km² from 1757.60 km² to 1488.43 km². The most significant decline trend was found during the period of 1995 and 2000, with a total decrease area of 281.43 km² and the lake dynamic change degree reached 2.78%. During this period, natural factors played a relatively small impact on changes of lake area, while human activities such as population growth, reclamation and construction of water conservancy projects became the dominant factor in the evolution of Lake Hongze.