Knowledge systems—networks of linked actors, organizations, and objects that perform a number of knowledge-related functions that link knowledge and know how with action—have played a key role in fostering agricultural development over the last 50 years. We examine the evolution of the knowledge system of the Yaqui Valley, Mexico, a region often described as the home of the green revolution for wheat, tracing changes in the functions of critical knowledge system participants, information flows, and research priorities. Most of the knowledge system's key players have been in place for many decades, although their roles have changed in response to exogenous and endogenous shocks and trends (e.g., drought, policy shifts, and price trends). The system has been agile and able to respond to challenges, in part because of the diversity of players (evolving roles of actors spanning research–decision maker boundaries) and also because of the strong and consistent role of innovative farmers. Although the agricultural research agenda in the Valley is primarily controlled from within the agricultural sector, outside voices have become an important influence in broadening development- and production-oriented perspectives to sustainability perspectives.