Surgeons are at risk of burnout and depression, which can lead to medical errors, inefficiency, exhaustion, conflicts, and suicide. Significant challenges exist in sub-Saharan Africa that may increase the prevalence of burnout and depression, but no formal evaluation has identified stressors specific to this environment. A survey was distributed to all members of the College of Surgeons of East, Central, and Southern Africa (COSECSA). Burnout, depression, and stressors were assessed with validated measures: Maslach Burnout Inventory for Medical Personnel, Patient Health Questionnaire (PHQ) 9, and Holmes-Rahe Life Stress Inventory. There were 131 participants (98 African and 33 non-African surgeons). The incidence of moderate to severe depression was 48% (n = 63), and the incidence of burnout was as high as 38% (n = 48). There were no significant differences between African and non-African surgeons in marital status, number of children, partners in practice, or distribution of time. More African surgeons experienced birth of a child (18% versus 3%, P = 0.04) but had less workplace conflict (7.1% versus 10.7%, P = 0.045) than non-African surgeons. African surgeons more consistently felt they were positively influencing others (P = 0.008), enjoyed working with patients (P = 0.009), and were more satisfied (P = 0.04). For all surgeons, predictors of increased PHQ-9 depression were serious professional conflict (P = 0.02), difficulty accessing childcare (P = 0.04), and racial discrimination (P = 0.003). In the Maslach model, predictors of burnout were difficulty accessing childcare (P = 0.05) and denial of promotion based on gender (P = 0.006). Burnout and depression in surgeons practicing in East, Central, and Southern Africa are substantial. Despite significant challenges, African surgeons tended to have a more positive outlook on their work. Improvements can be made to reduce burnout and depression by focusing on work conditions, equality of promotion opportunities, workplace conflict management, childcare support, and increasing the numbers of surgeons in practice.