The ecological protection and restoration of China's national land space has entered the stage of systematic management and construction of "mountains-rivers-forests-farmlands-lakes-grasslands". A comprehensive zoning study on the ecological protection and restoration can provide spatial guidance for the implementation of the concept of systemic governance by correctly understanding the characteristics of the geographical combination of ecosystems and their differentiation. The current zoning research on ecological protection and restoration is gradually focusing on the integrity of ecosystems, but the dimension of ecosystem characterization is relatively single, leading to a limited comprehensive cognition of the spatial systemic nature of the country. This study constructs a multidimensional index system for the ecological protection and restoration zoning based on ecological security theory and a comprehensive ecosystem assessment framework, in order to improve the systematic and comprehensive cognition of territorial space. Using watershed as the basic unit, this study adopts a spatial clustering approach to delineate two levels of ecological protection and restoration zones based on the assessment of the current ecological background and degradation characteristics of the Guangdong-Hong Kong-Macao Greater Bay Area. The results show that:(1) The current ecological quality and degradation of each watershed vary greatly, and the spatial differentiation is also relatively obvious, but the current ecological quality shows a circled differentiation with high quality in the outer part and low quality in the middle. In contrast, the spatial distribution of ecological degradation is relatively dispersed. (2) Based on the spatial heterogeneity of the comprehensive ecological status index and first grade zoning index data, the study area can be divided into five spatially continuous first grade zones of ecological protection and restoration. Based on the spatial heterogeneity of the composite index of ecological degradation and second grade zoning index data, the study area can be divided into 11 categories and 29 secondary zones of ecological protection and restoration within the first grade zone. The research scheme of the study can provide an ecological zoning optimization path for the systematic management of "mountains-rivers-forests-farmlands-lakes-grasslands" on territorial space. It also provides spatial decision support for ecological protection and restoration in the study area.