There are few studies on the role of migration within sub-Saharan Africa and its relation to the development of mental illness. We investigated post-resettlement adaptation and mental health challenges of African refugees/migrants in Durban, South Africa. We interviewed 335 African help-seeking refugees/migrants for anxiety, depression (25-item Hopkins Symptom Checklist) and post-traumatic stress symptoms (30-item Harvard Trauma Questionnaire). Socio-demographic and migration history, focusing on post-migration circumstances and experiences of discrimination in the host country, were obtained. Association between migration and post-settlement factors and mental health outcomes were assessed using adjusted logistic regression models. Prevalence of mental distress was high: 49.4% anxiety, 54.6% depression and 24.9% post-traumatic stress symptoms. After adjustment for family separation since migration, recent arrival in South Africa was associated with increased risk for depression (aOR = 4.0, 95% CI:1.3-11.8) and post-traumatic stress (aOR = 5.2, 95% CI:1.7-15.9), while in unadjusted models, older age on arrival was associated with anxiety (aOR = 5.3, 95% CI:1.4-19.8) and depression (aOR = 6.2, 95% CI:1.6-24.3). History of family separation since migration was independently associated with depression and post-traumatic stress in all models. Discriminatory experiences since migration was also an independent risk factor for all three mental health outcomes. Finally, being divorced/widowed was associated with an increased risk for post-traumatic stress, while higher income earners were protected against post-traumatic symptoms, even after adjustment. Refugees/migrants in South Africa show a significant burden of mental distress that is linked to challenges of adjustment in an often hostile context. Services addressing these and other health-related, social-economic needs should be developed as a priority.