Meeting the societal demand for food, bioproducts and water under climate change is likely to greatly challenge the maize-soybean agriculture of the Midwest USA, which is a globally significant resource. New agricultural systems are needed that can meet this challenge. Innovations in water management engineering and cropping system diversification may provide a way forward, enabling transformation to highly multifunctional agricultural watersheds that expand both agricultural production and water-related services to society, and which provide scalable units of climate adaptation in agriculture and water systems. Implementation and refinement of such watersheds require corresponding social innovation to create supportive social systems, in economic, political and cultural terms. A range of emerging social innovations can drive the emergence of highly multifunctional agricultural watersheds, by enabling robust cooperation, resource exchange and coordinated innovation across multiple societal sectors and scales. We highlight relevant innovations and opportunities for their exploratory implementation and refinement in the Midwest.