Knowledge is a critical enabling factor for healthy agri-food innovation systems (AIS). AIS and related knowledge management (KM) frameworks face significant implementation challenges. We review applications of KM to AIS, the current state of the art and shortcomings and present a new KM framework, Agricultural Knowledge Management for Innovation (AKM4I). Previous agricultural KM frameworks do not integrate innovation pragmatically, use linear, reductionist, top-down pathways to innovation, and do not explicitly incorporate issues of power, politics, ownership, and trust when combining scientific and local knowledge across multiple stakeholders. The AKM4I framework addresses systemic interactions favouring innovation outcomes by formalising flows and management of information and knowledge between diverse sets of stakeholders; and explicitly considering previously unresolved practical and relational barriers aiming to facilitate more equitable, rapidly evolving, and actionable knowledge generation and management for innovation and transformational change. An agricultural case study serves as an example of the implementation of AKM4I.