Abstract Climate-related risks in Central and South America have received increased attention and concern in science and policy, but an up-to-date comprehensive review and synthesis of risks and adaptation potential is currently missing. For this paper we evaluated over 200 peer-reviewed articles and grey literature documents published since 2012. We found that climate change in Central and South America during the 21st century may increase the risk to severe levels for the following topical risk clusters: (a) Food insecurity; (b) Floods and landslides; (c) Water scarcity; (d) Epidemics of vector-borne diseases; (e) Amazon Forest biome shift; (f). Coral bleaching; (g) Coastal risks of sea level rise, storm surges and erosion; (h) Systemic failure due to cascading impacts of hazards and epidemics. Our synthesis also identified feasible adaptation measures for each risk. The impacts of the risks will be heterogeneous throughout the region, with rural communities, Indigenous peoples, Afro-Latin Americans, women, disabled people, and migrants identified as being the most severely affected. We refer to a number of adaptation options for each risk. However, unabated climate change together with low adaptive capacity will strictly limit adaptation options. Immediate strengthening of policies for building adaptive capacity and increase of research on the risk-adaptation nexus in Central and South America are paramount. Our findings might contribute to guide the adjustment and emphasis of adaptation policies and climate risk management strategies from local to national level.