Shanghai is a cosmopolitan city and one of the most important economic centers in China, but is saddled with serious environmental problems resulting from a recent industrial transformation. This paper examines the interactive relationships between economic growth, eco-efficiency of urban metabolism, and environmental performance of the Shanghai metropolitan area since the 1990s using 15 indicators. This study has revealed an enhanced eco-efficiency of water and energy use as well as an improved overall environmental quality in the central urban districts of Shanghai. Both TGDP (total GDP) and GDP per capita increased rapidly at the annual rate of 16.28% and 15.91%, respectively. In contrast, energy consumed per 10,000 RMB YUAN GDP (ECG), water consumed per 10,000 RMB YUAN GDP (WCG), wastewater discharged per 10,000 RMB YUAN GDP (WWDG), and waste gases emitted per 10,000 RMB YUAN GDP (WGEG) decreased at the annual rate of 9.34%, 10.69%, 14.57%, and 8.52%, respectively. The rapid decline in ECG, WCG, WWDG, and WGEG indicates an enhanced eco-efficiency of urban metabolism. However, uncontrolled emission of wastes from domestic instead of industrial sources adversely affected the overall environmental quality. In addition, suburban areas have undergone rapid economic growth at the cost of human health deterioration, as measured by mortalities and relative mortality ratios of three major diseases (tumor, respiratory disease, and trauma/toxicosis). With Shanghai serving as the "locomotive" driving the economy of the Yangtze River Basin, effective pollution control policies and a network of regional coordination are urgently needed in the globalization and ecological security of the entire area.