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Summary: Background: Prospective data spanning childhood and adolescence are needed to better understand obesity incidence among children and to identify important periods for intervention. Objective: To describe gender differences in overweight and obesity from infancy to late adolescence in a South African cohort. Methods: We analysed body mass index at 1–2 years, 4–8 years, 11–12 years, 13–15 years and 16–18 years among 1172 participants in the South African Birth‐to‐Twenty cohort. Results: Among boys, overweight and obesity prevalence declined from age 1–2 years to 16–18 years. Among girls, overweight and obesity prevalence increased from 4–8 years to 16–18 years. Obesity incidence was highest from 4–8 years to 11–12 years in boys (6.8 cases per 1000 person‐years) and from 11–12 years to 13–15 years in girls (11.2 cases per 1000 person‐years). Among girls, obesity at 16–18 years was associated with overweight (odds ratio [OR] = 3.6; 95% confidence interval [CI] 1.8–7.2) or obesity (OR = 8.0; 95% CI 3.7–17.6) at 1–2 years and overweight (OR = 6.8; 95% CI 3.3–13.9) or obesity (OR = 42.3; 95% CI 15.0–118.8) at 4–8 years; for boys, obesity at 16–18 years was associated with overweight at 1–2 years (OR = 5.6; 95% CI 1.7–18.0) and obesity at 4–8 years (OR = 19.7; 95% CI 5.1–75.9). Conclusions: Among girls, overweight and obesity increased throughout childhood. Overweight and obesity were not widely prevalent among boys. Early childhood and post‐puberty may be important periods for intervention among girls. [ABSTRACT FROM AUTHOR]