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Crop wild relatives (CWR) are wild plant taxa that have broader genetic diversity than crops hence they are an excellent source of genes and traits to improve crops. The potential value of CWR for agriculture and the need to protect these plants in their natural habitats (in situ) have been recognized globally. South Africa has the richest temperate flora globally, and the checklist of food and fodder CWR for the country considers 258 taxa to be high priority for conservation. A systematic conservation planning approach was used for spatial prioritization for in situ conservation actions for CWR. Protected areas were categorized on the basis of their CWR richness. The Kruger National Park has the highest number of CWR (66 taxa), but most of these are widespread and common. Fifty-seven protected areas, most of which are in the Western and Eastern Cape fynbos, are irreplaceable for protecting a number of endemic and threatened CWR. For priority CWR not adequately represented in existing protected areas, a spatial plan was developed to identify the smallest area that aligns with existing targets for the National Protected Areas Expansion Strategy, that are not transformed in terms of habitat, and that are projected to be climate change resilient. Mechanisms for ensuring uptake of the recommendations for the in situ conservation of CWR have been documented in a National Strategy and Action Plan and these include making information and data available and promoting the inclusion of CWR in current management and monitoring activities.