The Detroit River has a long history of human use and abuse, resulting in public outcry over water pollution and resource degradation. This public outcry helped catalyze the enactment of many laws and the Canada-U.S. Great Lakes Water Quality Agreement which led to enhanced research, monitoring, and water pollution control. As pollution from industries and municipal wastewater treatment plants came under control and progress was made in management of single species, the focus shifted to a more comprehensive ecosystem approach that accounted for all the sources of pollution and targeted restoring ecosystem health with resilience. Over time, the Detroit River became a “proving ground” or crucible for experimenting with boundary organizations to overcome geographical, political, institutional, and disciplinary boundaries and strengthen science-policy-management linkages for ecosystem-based management. This study identified 15 boundary organizations functioning in the Detroit River watershed and evaluated two case studies – St. Clair-Detroit River System Initiative and State of the Strait Conferences. Key lessons learned from this study include: 1) establishing boundary organizations, promoting cooperative learning, and building capacity for boundary-spanning are essential for use of an ecosystem approach; 2) boundary spanning requires specific skills, experience, and improved linkages between research and practice; 3) the 15 boundary organizations provide a unique opportunity to collaborate in a community of practice to share knowledge, foster cooperative learning, enhance problem-solving, build trust, and demonstrate leadership; and 4) continued actionable science, investment in capacity building, and cooperative learning are essential to meet long-term goals of sustainability.