Psychological distress (PD) may be common among adolescents. The study aimed to estimate population-based rates of PD among adolescents in South Africa. National cross-sectional data were analysed from 2,240 adolescents (17 years median age) that participated in a community-based population survey, the “2012 South African National Health and Nutrition Examination Survey (SANHANES-1).” Results indicated that 16.0% of the adolescents had PD, 13.1% among boys and 18.5% among girls. In adjusted logistic regression analysis, increasing age, girls, belonging to the Black African population group, having experienced two or more traumatic life events, poor self-rated health status, having activity limitations, perceived body overweight, fast food and snack consumption were associated with PD. Almost one in six adolescents in South Africa reported PD and several associated factors were identified.