Evapotranspiration is an important part of the hydrological cycle, surface energy balance and global climate system. Due to spatial heterogeneity, the trends in actual evapotranspiration (ET) and its associated factors vary in different regions. Because direct measurements of ET are limited over large areas, remote sensing provides an efficient method of ET spatial analysis, and standard data products are available at the global scale. This study uses the monthly MOD16 ET dataset and daily meteorological data to analyze the dynamic spatiotemporal changes in ET and its associated factors in the Pearl River Basin (PRB) from 2000 to 2014. The results of the study are as follows. (1) Over time and space, annual ET exhibited a slight increasing trend from 2000 to 2014, with an average value of approximately 946.56 mm/a. ET considerably varied at the monthly and seasonal scales, and in July displayed the highest monthly ET of approximately 119.57 mm, accounting for 36.37% of the annual ET. (2) ET displayed obvious spatial heterogeneity. Specifically, the west was a low-ET region, and moderate and high ET values were interspersed in the central and eastern PRB. Moreover, the rate of change of ET ranged from −13.99 mm/a to 12.81 mm/a in space, and 46.25% of the basin exhibited an increasing trend. (3) Dynamic changes in ET were mainly associated with temperature and relative humidity (RH). Additionally, energy-related elements and wind speed were positively correlated with ET, and temperature was the most influential factor of ET in some months (February–March and September–November). RH was the most important factor in other months but negatively correlated with ET in June and July. Affected by the actual environmental condition, qualitative changes were observed in the correlation between RH and ET in different months. The positive and negative spatial correlations between ET and its associated factors changed in different regions and in different months, and the changes mainly occurred from northwest to southwest.