Rapid economic development and population growth in China’s Yangtze River Delta (YRD) are exerting significant environmental pressure on the region’s land and water, especially in hilly areas where many drinking water reservoirs have been constructed. These areas, which are characterized by steep slopes and thin soils, provide critical services, including flood control, water resource supply, food production, and recreational opportunities for nearby highly developed and heavily populated areas of the delta. We contrast two of these areas—the well-studied Tianmu Lake watershed and the much larger Qiandao Lake watershed. Both face similar challenges from nitrogen and phosphorus pollution due to rapid socio-economic development, but differences in watershed size and distinctions related to political boundaries influence the range of approaches available to maintain water quality. We review experiences of controlling nutrient pollution in these watersheds as case studies, and based on that information, propose an integrated framework to minimize nitrogen and phosphorus pollution in similarly challenged watersheds. The framework, which is designed to be generalizable rather than prescriptive, emphasizes source control, delivery interception, and fate management of nutrients.