Inland lakes are vital components of the water resource system. They not only maintain regional ecological balance but also serve as indicators of climate change and human activities. In this study, the Google Earth Engine (GEE) remote sensing cloud platform was used, and JRC (JRC Global Surface Water) water body data was used as the main data source. Pearson correlation analysis and time geographic weighted regression (GTWR) were used to study the spatial and temporal dynamic changes of the number and area of lakes in the Mongolia-Xinjiang Plateau from 1989 to 2021, and the main reasons for the changes in lakes in the Mongolia-Xinjiang Plateau were quantitatively analyzed. The results showed that the number and area of lakes on the Mongolia-Xinjiang Plateau had increased significantly in the past 33 years. The area and number of small lakes (1-10 km²) accounted for the largest proportion and the most significant increase, followed by medium-sized lakes (10-100 km²) and large lakes (>100 km²). In all elevation zones, lakes generally showed a trend of expansion. The changes in lakes in low-altitude areas (DEM≥1500 m) were significantly affected by temperature and precipitation and showed consistency in different vertical zones. The lakes in 14 basins in the lake area expanded, of which 8 basins expanded significantly. Due to strong human activities and the impact of climate change, the lakes in the eastern Erguna River Basin and the inland river basin of the Inner Mongolia Plateau shrank significantly. Mastering the temporal and spatial variation characteristics and related causes of lakes in the Mongolia-Xinjiang Plateau provided a theoretical reference for climate change and water resource protection in China's arid and semi-arid regions and even the world.