[Objective] The driving forces of the spatial distribution and spato-temporal changes in fractional vegetation coverage (FVC) in the Pearl River delta were analyzed in order to provide a scientific reference for the protection of the ecological environment in the region. [Methods] A binary pixel model was used with Landsat 5 TM and Landsat 8 OLI data to invert the vegetation coverage of the Pearl River delta in 2000, 2005, 2010, 2015, and 2020. The spatial pattern and spatio-temporal changes in FVC in the Pearl River delta were analyzed. Annual precipitation, average annual temperature, population density, and land use data during the five study periods were analyzed using correlation coefficients and the geographical detector method. [Results] ① Vegetation coverage in the Pearl River delta was lower in the middle of the region and higher in the marginal regions. Vegetation coverage was lower in Foshan, Zhongshan, Zhuhai, Southwestern Guangzhou, Dongguan City, and Shenzhen City, and higher in Zhaoqing, Jiangmen City, and Huizhou City. Overall, vegetation coverage increased over time, with 64.99% of the total area showing increases in vegetation coverage. There were stage differences in time, and the area with highest vegetation coverage (more than 80%) increased most significantly during 2010-2015. ② There were obvious regional differences in the driving factors of FVC. Annual precipitation and land use had more inhibiting effects than promoting effects, and average annual temperature and population density had more promoting effects than inhibiting effects. ③ The spatial pattern factor detection of FVC showed that the explanatory power of land use degree was the strongest, while the interactive detection showed that the explanatory power of annual average temperature and land use degree interaction was the highest. For the explanatory power of annual precipitation, annual precipitation and annual temperature interaction showed a weakening trend in the time series of 2000, 2005, 2010, 2015, and 2020. The explanatory power of other influencing factors and their interactions showed an increasing trend. The spatial-temporal FVC change factor detection also indicated that the explanatory power of land use degree change was the strongest, while the interactive detection indicated that annual precipitation change and land use degree interaction had the highest explanatory power. [Conclusion] Land use degree was the dominant factor affecting the temporal and spatial changes of vegetation coverage in the Pearl River delta. Human influence continues to increase, and the interaction of the two factors is significantly greater than the effect of a single factor.