The apartheid regime that governed South Africa from 1948 – 1994 established spatial segregation that is understood to have contributed to the magnitude of neighborhood social disorder in the post-apartheid era. Although a number of neighborhood social disorder characteristics, such as perceived violence and crime in the community, are prominent issues in South Africa, the extent to which these perceived spatial attributes are linked to depression is unknown at the population-level. Multilevel modeling of data from the second wave of the South African National Income Dynamics Study (SA-NIDS) was utilized to examine the relationship between depressive symptomatology and neighborhood social disorder as indicated by the perceived frequency of violent, criminal and illicit activities in the community. Depressive symptomatology was assessed using the 10-item version of the Center for Epidemiologic Studies Depression Scale. A cut off score of ten or higher was used to indicate the presence of significant depressive symptomatology. Results showed that perception of neighborhood social disorder was independently associated with significant levels of depressive symptomatology. Gender, race/ethnicity, perceived health status, and education were significant for individual-level covariates of depression. Community intervention strategies that reduce the risk of neighborhood disorganization and emphasize positive social norms in the neighborhood are warranted. Taking into account the residential de-racialization of a country transitioning from apartheid to non-racial democracy, a longitudinal spatial study design assessing the dynamics between depression and the aforementioned perceptions of neighborhood attributes may also be warranted.