In the National Strategy of the Guangdong-Hong Kong-Macao Greater Bay Area, Guangdong Province assumed the function of the ecological protection barrier, and vegetation played an irreplaceable role in regional ecological security and sustainable development as an important regional ecological barrier. It was significant to study the change of fractional vegetation coverage (FVC) in Guangdong Province and its response to land-use change. Based on the MODIS-NDVI remote sensing index from 2000 to 2020, the study used dimidiate pixel model to extract FVC, trend analysis and significance test were used to analyze the temporal and spatial characteristics of FVC and to clarify driving forces of land-use change, which was expected to provide theoretical support and scientific basis for the construction of ecological security pattern and sustainable development decision-making in Guangdong Province. Results showed that (1) the FVC presented a volatility increasing trend with the change rate of 0.23% per year from 2000 to 2020. However, the spatial heterogeneity of FVC dynamic was significant, showing a center of the Pearl River Delta with an increasing trend of outward radiation. (2) The annual average vegetation coverage in Guangdong Province ranged from 0.7 to 0.76, which was dominated by the medium to high and high FVC types, while the areas of low FVC only accounted for about 4.37% of the study area, it was closely related to the regional differences in the topography, land-use types, urbanization process and economic development level of Guangdong Province. The FVC improved areas occupied 78.18% of the study area, significant and very significant degenerated areas accounted for 5.84% of the region which were concentrated in the Pearl River Delta, the east coast and the west coast of Guangdong Province. (3) The major characteristics of land-use change were swaps between the geo-spectrum unit of arable land and forest land, and urban-rural construction land played an important role in the occupation and replenishment of arable land and forest land, which reflected the massive occupation of arable land and forest land in the process of urban and rural construction. There was a response link between FVC change and land-use change, and the contribution of each land-use type to vegetation coverage varied. The map of transformation to urban-rural construction land highly overlapped with the degenerated areas of FVC, which meant the conversion of arable land and forest land to urban-rural construction land was the main reason for the degradation of FVC, most notably in the Pearl River Delta.