‘Climate-smart agriculture’ (CSA)—agriculture and food systems that sustainably increase food production, improve resilience (or adaptive capacity) of farming systems, and mitigate climate change when possible—has quickly been integrated into the global development agenda. However, the empirical evidence base for CSA has not been assembled, complicating the transition from CSA concept to concrete actions, and contributing to ideological disagreement among development practitioners. Thus, there is an urgent need to evaluate current knowledge on the effectiveness of CSA to achieve its intended benefits and inform discourse on food, agriculture, and climate change. This systematic review intends to establish the scientific evidence base of CSA practices to inform the next steps in development of agricultural programming and policy. Evaluate the impact of 73 promising farm-level management practices across five categories (agronomy, agroforestry, livestock, postharvest management, and energy systems) to assess their contributions to the three CSA pillars: agronomic and economic productivity, resilience and adaptive capacity, and climate change mitigation in the developing world. The resulting data will be compiled into a searchable Web-based database and analytical engine that can be used to assess the relative effectiveness and strength of evidence for CSA, as well as identify best-fit practices for specific farming and development contexts. This represents the largest meta-analysis of agricultural practices to date.