Air pollution is a growing problem in developing countries, and there exists a wide range of evidence documenting the large health and productivity losses associated with high concentrations of pollutants. South Africa is a developing country with high levels of air pollution in some regions, and the costs of air pollution on human health and economic growth in South Africa are still uncertain. The environmental Benefits Mapping and Analysis Program (BenMAP) model was applied to South Africa using local data on population, mortality rates, and concentrations of fine particulate matter (PM2.5), as well as mortality risk coefficients from the epidemiological literature. BenMAP estimates the number of premature deaths that would likely have been avoided if South African air quality levels met the existing annual National Ambient Air Quality Standard (NAAQS) of 20 μg m-3, and the more stringent World Health Organization (WHO) guideline for annual average PM2.5 of 10 μg m-3. We estimate 14,000 avoided premature mortalities in 2012 if all of South Africa met the existing NAAQS annual average standard for PM2.5. These avoided cases of mortality have an estimated monetary value of $14.0 billion (US2011$), which is equivalent to 2.2% of South Africa's 2012 GDP (PPP, US2011$). We estimate 28,000 avoided premature mortalities if the more stringent WHO guideline for annual average PM2.5 is met across South Africa, which when expressed as a national burden is equivalent to 6% of all deaths in South Africa being attributable to PM2.5 exposure. These avoided cases of mortality have an estimated monetary value of $29.1 billion, which is equivalent to 4.5% of South Africa's 2012 GDP. These results show that there are significant public health benefits to lowering PM2.5 concentrations across South Africa, with correspondingly high economic benefits.