This Nature Food commentary proposes a transformative agricultural research paradigm centred on the concept of “crops that nourish”—crops and cropping systems that simultaneously enhance human nutrition, soil health, climate resilience, and local prosperity. Focusing particularly on sub-Saharan Africa, the authors argue that conventional yield-centric research has overlooked nutrition, agrobiodiversity, environmental sustainability, and local agency. They call for transdisciplinary, participatory action research that begins with community-defined priorities and integrates agronomic, nutritional, socioeconomic, and ecological goals. The article highlights “opportunity crops,” including neglected and underutilised species, as key leverage points for food system transformation due to their nutritional density, resilience to stress, and public and private benefits. Emphasis is placed on co-creation between farmers and researchers, participatory plant breeding, inclusive value-chain development, and clear impact pathways linking research to systems-level change. The authors conclude that empowering local communities, investing in African scientific capacity, and aligning research with policy, markets, and consumer demand are essential to building resilient, nutritious, and equitable food systems.