Background: The first Youth Risk Behaviour Survey in South Africa was carried out to establish the prevalence of key health risk behaviours among high school students. Though physical inactivity is a commonly reported contributory factor to chronic diseases of lifestyle in South Africa, there is no reliable national database on the participation of children and adolescents in physical activity. Methods: This cross-sectional national prevalence study among students attending government schools in the nine provinces in South Africa utilized a two-stage cluster sample design. Statistical analysis allowed for clustered sampling, and data collected through self-administered questionnaire were weighted to reflect the underlying student population. Results: Data of 10,699 participants were analyzed. More than one third (37.5%) of the students engaged in insufficient physical activity. By population group, a significantly lower proportion of white students (29.4%) than black (37.5%) and coloured students (45.6%) engaged in insufficient physical activity. Among those who abstained from participation, 25.9% were unwilling to participate, with significantly fewer white (26.8%) and black (25.1 %) students feeling unsafe in their surroundings compared with coloured students (35.3%). Significantly fewer white students (5.6%) had no access to facilities compared to black students (17.0%). White students and students in higher grades reported lower rates of physical education classes at school. Interpretation: Though the promotion of physical activity and healthy lifestyle is a national priority in South Africa, the survey indicates the need to pay attention to an appreciable proportion of high school students who do not participate sufficiently in physical activity.