<p>Understanding ecosystem service (ES) supply-demand relationships and spatial characteristics is essential for effective ecosystem management and sustainable development. However, current ecosystem management in many provinces of China still relies largely on broad, top-down ecological policies that often overlook local socio-ecological heterogeneity. Consequently, differentiated ecological management approaches that integrate spatially explicit ES supply–demand dynamics with regional ecological functions remain insufficiently developed. Focusing on Guangdong Province, China, this study evaluated the supply and demand of four critical ecosystem services—crop production, water conservation, soil retention, and biodiversity maintenance—at the county level. The interrelationship between different ESs was further explored with multiple spatial analysis tools. Based on these interactions and key ecological functions, we developed an ecological zoning framework and proposed relevant management strategies. The results were as follows: (1) ES supply and demand displayed significant spatial heterogeneity. Water conservation and soil retention showed higher supply in western Guangdong and lower in eastern Guangdong, whereas ES demand was strongly concentrated in coastal plains and Pearl River Delta (PRD); (2) Except for the overall surplus in water conservation and soil retention, the mismatch between ES supply and demand was evident, particularly in highly urbanized regions and biodiversity maintenance showing the greatest heterogeneity; (3) Two ecological zoning schemes were developed based on ES supply-demand relationships and key ecological functions. The integrated results identified seven major ecological management zones, including the Ecological Industry Improvement Area, the Ecological Characteristic Development Area, the Ecological Core Protection Area, the Highly Urbanized and Key Ecological Restoration Area, the Potential Urban Development and Ecological Restoration Area, the Ecological and Economic Reconstruction Area and the Ecological and Economic Enhancement Area. Differentiated and targeted management strategies were proposed for each zone. Overall, the findings provide a spatially explicit basis for refining ecological zoning in Guangdong and support the development of differentiated, place-based management strategies that enhance both ecological function and regional sustainability.</p>