Providing universal food security and conserving biodiversity are prominent challenges facing humanity in the 21st century. Typically, these challenges are believed to involve a trade-off, especially in farming landscapes of the Global South. We conducted a multivariate analysis of social-ecological data from 110 landscapes in the Global South, and found that different system characteristics lead to partly predictable outcomes, resulting either in trade-offs or, unexpectedly, in synergies (mutual benefits) between food security and biodiversity. Specifically, these synergies are fostered by social equity, by reliable access to local land, and by increasing social capital (eg maintenance of traditions) and human capital (eg health). In contrast, we also found high degrees of food security in landscapes with adequate infrastructure, market access, and financial capital, but this increased security came at the expense of biodiversity. Our findings demonstrate that a social-ecological systems perspective can help to identify previously unrecognized synergies between food security and biodiversity conservation.