BackgroundSouth Africa has undergone major economic and health system changes impacting the epidemiology of childhood asthma. This study aimed to investigate prevalence time-trends of asthma in South African adolescents over 2 decades and to identify associated risk-factors.MethodsA cross-sectional survey was conducted in 2017, in a randomised sample of 13–14 year-old Cape Town adolescents, using the standardised Global Asthma Network written, video, and environmental questionnaires. Using time-trend analysis, the prevalence and severity of asthma were compared with data from the 2002 ISAAC phase III study. Environmental and social risk-factors were analysed.Results3979 adolescents were included. Prevalence of lifetime and current asthma were 34.5% and 21.3%, respectively, on the self-report written questionnaire, similar to 2002 results. The prevalence of severe asthma in the last 12 months increased, measured by wheeze limiting speech (7.8% to 11.8%), ≥4 attacks of wheezing (5.0% to 5.8%) or ≥1 night·week−1 waking from wheezing (5.0% to 6.9%). The video questionnaire revealed increases in lifetime (16.9% to 22.5%), current (11.2% to 18.7%), or severe asthma (12.1% to 14.8%). Multivariate analysis showed associations between current asthma and smoking, female sex, pet exposure or higher socioeconomic status. Severe asthma was associated with smoking, pet exposure, outdoor pollution exposure or informal housing. 33% of those with severe or current asthma had been diagnosed.ConclusionThe prevalence of asthma is high, with increasing rates of severe asthma in adolescents. Underdiagnosis is a major concern and reduction in exposure to environmental factors, particularly smoking, and improved socioeconomic development are needed.