Analyzing vegetation coverage and land-use and land cover (LULC) characteristics helps to understand the interaction between human activities and the natural environment. The coastal regions of the Guangdong Province are economically active areas with frequent human activities, located in the advantageous natural environment of South China. This study analyzed the spatiotemporal characteristics of the normalized difference vegetation index (NDVI) and LULC from 2000 to 2020, to explore the response of NDVI changes to LULC changes. The results show that (1) the overall NDVI is relatively high, with a proportion of 85.37% to 89.48% of areas with higher coverage and above categories, mainly distributed in the east and west. Vegetation coverage showed an increasing trend. (2) The LULC in this area is mainly composed of forest land (46.5% to 47.5%) and cultivated land (30.7% to 33.4%), with forest land mainly distributed in relatively high-altitude regions and cultivated land mainly distributed in the plains. The changes in LULC from 2015 to 2020 were relatively significant, mainly due to the mutual transfer of cultivated land and forest land. In addition, built-up land continued to expand from 2000 to 2020, mainly in the Pearl River Delta. (3) The NDVI decreases come from the transfer of various types of land to built-up land, mainly in the Pearl River Delta region, while the NDVI increase comes from the stability and mutual transfer of cultivated land. The net contribution rate of forest land change to vegetation cover change is the most significant (−38.903% to 23.144%). This study has reference significance for the spatiotemporal characteristics of vegetation cover changes in coastal areas and their response to land-use changes, as well as coastal management and sustainable development.