BACKGROUND: The Center for Epidemiologic Studies-Depression (CES-D) scale is a widely used measure of depressive symptoms, but its construct validity has not been adequately assessed in sub-Saharan Africa. This study validates the CES-D among an aging Shangaan-speaking and predominantly Black African sample in rural South Africa, with a special emphasis on gender differences. METHODS: An 8-item CES-D scale was administered in Shangaan to 5059 respondents, aged 40+ years, residing in Agincourt, South Africa. We used Cronbach's alpha and exploratory and confirmatory factor analysis to examine and confirm dimensionality of the CES-D scale. Differential endorsement of CES-D items by gender were assessed using the Mantel-Haenszel (MH) odds ratio test. RESULTS: Reliability of the CES-D scale differed by gender with women reporting higher internal consistency on items than men. A two-factor solution was retained and confirmed representing two latent factors: (1) Negative Affect (six items) and (2) Diminished Positive Affect (two items). MH results showed that men exhibited significantly higher odds of putting an effort in everything that they did (OR: 1.33, 95% CI: 1.15-1.54) and lower odds of feeling depressed (OR: 0.71, 95% CI: 0.56-0.89) and having restless sleep (OR: 0.67, 95% CI:0.58-0.77) than women. LIMITATIONS: Analyses were limited to a dichotomous, short form of the CES-D, a self-reported population-based measure. CONCLUSION: Aging Black Africans differ in endorsing affective and somatic items on the CES-D scale by gender, which may lead to skewed population-level estimates of depression in key subpopulations. These findings highlight the importance of continued research disentangling cross-cultural and gendered nuances of depression measurements.