Karst rocky desertification is a progressive process of land degradation in karst regions in which soil is severely, or completely, eroded. This process may be caused by natural factors, such as geological structure, and population pressure leading to poor ecosystem health and lagging economic development. Karst rocky desertification is therefore a significant obstacle to sustainable development in southwest China. We applied a radial basis function network model to assess the risk of karst rocky desertification in northwest Guangxi, a typical karst region located in southwest China. Factors known to influence karst rocky desertification were evaluated using remote sensing and geographic information systems techniques to classify the 23 counties in the study area from low to extreme risk of karst rocky desertification. Counties with extreme or strong karst rocky desertification risk (43.48%, nearly half of the study area) were clustered in the north, central and southeast portions of the study area. Counties with low karst rocky desertification (30.43%) were located in the west, northeast and southwest of the study area. The spatial distribution of karst rocky desertification was moderately correlated to population density.