The objective of this forward-looking synthesis was to bring together learning from a decade of experience with CGIAR research programs (CRPs), based on existing evaluative evidence. The purpose of this meta-review is to review lessons from the CRP experience to inform the development of future research programs of One CGIAR. The 2021 Synthesis and Lessons Learned from a Decade of CRPs is delivered in response to the request of the CGIAR System Council and aligned with the synthesis terms of reference endorsed by SIMEC in February 2021. The synthesis examined evidence from the two phases of CRP implementation: 2011–2016 and 2017–2019. Four key issues were addressed: (1) patterns and trends between the two phases of CRPs related to the quality of science (QoS) and research for development, achievement of sustainable development outcomes, and management and governance; (2) systemwide issues affecting CRP achievements; (3) recommendations for the future orientation of CGIAR research and innovation; and (4) key evidence gaps and needs for future evaluations. A narrative synthesis approach was used, employing secondary source data from 47 existing evaluations and reviews. External evaluations were systematically coded and analyzed by senior subject matter experts (SMEs) using a standardized analytical framework. A bibliometric trend analysis was carried out, and findings were triangulated against earlier syntheses and validated by members of the Independent Science for Development Council (ISDC), CRP leaders, and expert peer reviewers