Rapid urbanization in China has profoundly transformed its urban systems, bringing about considerable ecological challenges and significant imbalances between urban growth and ecological health. The Pearl River Delta (PRD) urban agglomeration, as one of China’s most economically dynamic regions, exemplifies the complex interactions between rapid urbanization and environmental sustainability. This study examined these dynamics using statistical yearbook and geographic information data from 1999 to 2018. Through a multi-scale approach integrating panel entropy, coupled coordination analysis, and FLUS models, we evaluated the relationship between urbanization and ecology at both the agglomeration and city levels. The findings revealed that while the overall coordination between urbanization and ecology in the PRD has improved, it remains at a moderate level with pronounced core-periphery disparities. Core cities face increasing ecological pressures and inefficient land use patterns. Simulation results, under three distinct policy scenarios—“unconstrained”, “growth machine”, and “compact and intensive usage/urban renewal”—and validated through field research, indicate that urban renewal presents a viable strategy for optimizing land use and mitigating ecological pressures. The study provides both a comprehensive diagnostic framework for assessing urban health and sustainability and practical intervention pathways, particularly for regions experiencing similar rapid urbanization challenges. The insights gained are especially relevant to other developing countries, offering strategies to enhance urban resilience and ecological sustainability while addressing persistent regional inequalities.