To investigate the spatiotemporal variability of water use efficiency(WUE) in the terrestrial ecosystem of Guangdong Province and its response to environmental changes, WUE in the terrestrial ecosystem of Guangdong Province from 2000 to 2020 was calculated based on satellite remote sensing data from MODIS. With refined rainfall, temperature, and soil moisture data products, six interannual change types of WUE in Guangdong Province were identified, and the potential impacts of ecosystem carbohydrate flux changes on WUE of the major change types caused by environmental factors were evaluated using trend analysis, partial correlation analysis, and the maximal value composite method. The results demonstrate that WUE in the terrestrial ecosystem of Guangdong Province shows different trends across the region, with increasing trends dominating in western Guangdong and the southern Pearl River Delta, and decreasing trends dominating in eastern Guangdong, northern Guangdong, and some areas of the Pearl River Delta. The differences in the trends of WUE are mainly due to different growth rates of gross primary productivity (GPP) and actual evapotranspiration (AET). UUU and DUU are the two main interannual change types of WUE. For the UUU change type, the temperature factor drives GPP of savanna and farmland ecosystems, making its growth rate greater than that of AET, resulting in an overall increasing trend in WUE. For the DUU change type, the precipitation and soil moisture factors drive AET of forest, woody savanna, and savanna ecosystems, making its growth rate greater than that of GPP, resulting in an overall decreasing trend in WUE.