The widely distributed lakes, as one of the major components of the inland water system, are the primary available freshwater resources on the earth and are sensitive to accelerated climate change and extensive human activities. Lakes play an important role in the terrestrial water cycle and biogeochemical cycle and substantially influence the health of humans living in the surrounding areas. Given the importance of lakes in the ecosystem, long-term monitoring of dynamic changes has important theoretical and practical significance. Here, we extracted water body information and monitored the long-term dynamics of Bosten Lake, which is the largest inland lake in China. We quantified the meteorological factors of the study area from the observation data of meteorological stations between 1988 and 2018. The characteristics of climate change and its correlation with the change of area in the Bosten Lake Basin in the past 30 years were analyzed. The major contributions of this study are as follows: (1) The initial water body was segmented based on the water index model Normalized Difference Water Index (NDWI) and Modified Normalized Difference Water Index (MNDWI) with a pre-assigned threshold value. The results were evaluated with the area extracted through artificial visual interpretation. Then we conducted mathematical morphology operators, opening and closing operations, and median filter to eliminate noise to ensure the accuracy of water body information extraction from the Bosten Lake. A long-term water surface area database of the Bosten Lake was established from high-resolution remote sensing images during 1988–2018. (2) Due to the seasonal difference of snow, ice content, and other objects on images, the areadynamics of Bosten Lake in the recent 30 years were analyzed separately in dry season and rainy season. The water surface area of Bosten Lake showed large inter-annual variations between 1988–2018. (3) Based on the assumption that climatic change has more direct effects on lake than human activities, six meteorological factors were selected to analyze the impacts of climate change on the annual mean lake surface area. The result indicated that in the past 30 years, climate conditions in the Bosten Lake Basin fluctuated greatly. We conducted correlations analysis between the areal dynamics of the Bosten Lake and the meteorological factors. Here, the annual average evaporation had the highest correlation with the areal dynamics of Bosten Lake followed by air temperature, precipitation, sunshine hours, and relative humidity, while the annual average wind speed had the weakest correlation.