Global food security is under threat by climate change, and the impacts fall disproportionately on resource-poor small producers. With the goal of making agricultural and food systems more climate-resilient, this paper presents an adaptation and mitigation framework. A road map for further agricultural research is proposed, based on the CGIAR Research Program on Climate Change, Agriculture and Food Security. We propose a holistic, integrated approach that takes into account trade-offs and feedbacks between interventions. We divide the agenda into four research areas, three tackling risk management, accelerated adaptation and emissions mitigation, and the fourth facilitating adoption of research outputs. After reviewing specific technical, agronomic and policy options for reducing climate change vulnerability, we acknowledge that science and good-faith recommendations do not necessarily translate into effective and timely actions. We therefore outline impediments to behavioural change and propose that future research overcomes these obstacles by linking the right institutions, instruments and scientific outputs. Food security research must go beyond its focus on production to also examine food access and utilization issues. Finally, we conclude that urgent action is needed despite the uncertainties, trade-offs and challenges.