Efforts to create a more sustainable world present extraordinary leadership and research opportunities for knowledge institutions, including universities, science centers, and government science programs. The rapid evolution of sustainability-related initiatives at such institutions also provides an outstanding opportunity for learning how to design and manage interdisciplinary research and researcher-stakeholder partnerships, so that scientific knowledge can be linked with societal action. Using carefully selected institutions to illustrate variation, our symposium examines the relationship between the institutional structure of knowledge organizations and the sustainability-related outcomes we can expect from those organizations. We focus particularly on several key characteristics that influence the potential roles such institutions play in understanding and solving sustainability problems: first, the history and culture of the institution, including its public versus private status; second, the role of leadership, including top-down versus bottom-up approaches to decision-making and innovation; third, strategies for boundary management, including the extent and mode of researcher engagement with stakeholders; and fourth, the focal geographic and political scales of the institution’s research and partnerships. The results of this comparative assessment can be used to develop models and best practices for transforming knowledge institutions to better achieve our common societal goals and aspirations.