South Africa has an important responsibility to global biodiversity conservation, but a largely inadequate conservation area network for addressing this responsibility. This study employs a coarse-filter approach based on 68 potential vegetation units to identify areas that are largely transformed, degraded, or impacted upon by road effects. The assessment highlights broad vegetation types that face high biodiversity losses currently or in the near future due to human impacts. Most vegetation types contain large tracts of natural vegetation, with little degradation, transformation, or impacts from road networks. Regions in the grasslands, fynbos, and forest biomes are worst affected. Very few of the vegetation types are adequately protected according to the IUCN’s 10% protected area conservation target, with the fynbos and savanna biomes containing a few vegetation types that do achieve this arbitrary goal. This investigation identifies areas where limited conservation resources should be concentrated by identifying vegetation types with high levels of anthropogenic land-use threats and associated current and potential biodiversity loss.