PURPOSE: The aims of this study were to (a) describe gender inequalities in physical activity (PA) among adolescents from Global South countries, and (b) investigate the relationship between gender inequalities in PA and contextual factors, such as geographic region, human development index, gender inequality index, and unemployment rates. METHODS: We analyzed cross-sectional data from the Global School-Based Student Health Survey conducted in Global South countries between 2010 and 2020 among 13- to 17-year-old adolescents. Country-context variables were retrieved from secondary data sources (World Health Organization, World Bank, and Human Development Reports). PA was assessed by a self-administered questionnaire querying the number of days in the past week in which participants were physically active for a total of at least 60 min. PA absolute gender inequalities were evaluated by the differences in the prevalence between boys and girls, 95% confidence intervals (95%CIs) were estimated using the bootstrap method. Relative inequalities were obtained through Poisson regression. Meta-analyses with random effects were used to calculate pooled estimates of absolute and relative inequalities. RESULTS: Based on 64 Global South countries/surveys, the prevalence of PA was 6.7 percentage points (p.p.) higher in boys than in girls, ranging from 0.5 p.p. in Afghanistan to 15.6 p.p. in Laos (I2= 85.1%). The pooled ratio for all countries showed that boys presented a PA prevalence 1.58 times higher than girls (95%CI: 1.47-1.70) on average. The highest absolute and relative inequalities were observed in high income countries. Countries with higher Human Development Index rankings and lower Gender Inequality Index rankings also presented greater gender differences. CONCLUSION: Given that girls are overall less active than boys across the globe, the findings of this study reinforce that macro- and micro-level changes should be actively sought if we aim to increase population levels of PA in adolescents and promote equity in PA.