Few studies have examined depression among immigrants in post-apartheid South Africa, and factors that strengthen the relationship between immigration and depression. The first wave of the National Income Dynamics Study was used to investigate links between immigration and depression (n = 15,205). Depression symptoms were assessed using a 10-item version of the Center for Epidemiologic Studies Depression (CES-D) Scale. Immigrants in South Africa had fewer depressive symptoms (CES-D = 10) than locally-born participants (17.1 vs. 32.4 %, F = 13.5, p < 0.01). Multilevel mixed-effects logistic regression analyses found that among immigrant populations, younger age (adjusted OR 1.03, 95 % CI 1.01–1.05) and black African ethnicity (adjusted OR 3.72, 95 % CI 1.29–10.7) were associated with higher depression. Younger age was associated with lower depression among locally-born study participants (adjusted OR 0.98, 95 % CI 0.97–0.98). The varying relationship between certain demographic factors, depression and the different mental health challenges among these groups requires closer attention.