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Aim: The spatially varying prevalence and determinants of depression in the urban population of South Africa have remained unexplored. This study sets out to examine the spatial variations and determinants of depression status among the urban population of South Africa. Methods: Data were sourced from the Wave 5 of the National Income Dynamics Study (NIDS) of 2017, which was a survey of households and individuals aged 15 years and above living in the nine provinces of South Africa. The outcome variable is depression status. Data analysis involved descriptive statistics, mapping, and geographically weighted regression. Results: Results showed variations in the prevalence of depression status across the nine provinces of South Africa. The prevalence of low depression status ranged from 77% in Eastern Cape Province to 88% in Western Cape Province. In addition, the results revealed spatial variations across the provinces on the influence of socio-economic factors on depression status of the urban population in South Africa. Conclusion: This study recommends the development and implementation of unique effective approaches for prevention, mitigation, and management of depression problems for each of the provinces.