Lake surface water temperature (LSWT) has a significant impact on aquatic ecosystem. This study aimed to reveal the variations and driving factors of LSWT in Tonle Sap Lake, the largest freshwater lake in South Asia. For this purpose, the datasets of LSWT-day, atmospheric temperature (AT), lake surface area (LSA), watershed land use and cover change (WLUCC) were extracted based on MODIS products and AT images by remote sensing technology. Then, through GIS geospatial analysis technology and mathematical statistical methods, the spatial-temporal variations of LSWT-day, AT, LSA and WLUCC were analyzed, and the relationships between LSWT-day and AT, LSA, WLUCC were further discussed. Results showed that: 1) from 2001 to 2018, the annual mean LSWT-day and AT showed a significant warming trend. AT was a main driving factor affecting LSWT in Tonle Sap Lake. 2) LSA showed a slightly decreasing tendency and had an obvious negative correlation with LSWT-day, which was an important factor affecting LSWT. 3) WLUCC had undergone drastic changes and its influence on LSWT could not be ignored. In summary, this paper fills the gap of the long-term series of LSWT research in Tonle Sap Lake and enhances the understanding of LSWT changing mechanism for similar lakes.