The precursors of non-communicable diseases (NCDs) are often manifested during childhood and adolescence with little knowledge about co-occurrence of their related lifestyle risk factors. To address this deficit, we estimated the prevalence and clustering of six major NCD-risk factors in adolescents around the world. Data from the Global School-based Student Health Survey, collected between 2007 and 2016, were analysed in 304,779 adolescents aged 11–17 years (52.2% females) from 89 countries. We compared the observed (O) to expected (E) prevalence ratios of 64 possible combinations of six risk factors to determine their clustering patterns. Overall, 82.4% (95% CI 82.1–82.7) of adolescents had ≥2 risk factors, while 34.9% (34.6–35.3) had ≥3. Adolescents aged 16–17 years, compared to those aged 11–13 years, had higher odds (OR 1.33; 95% CI 1.31–1.36) of reporting ≥3 risk factors. Risk factors clustered in multiple combinations and differed by sex. The clustering of physical inactivity and low fruit and vegetable intake was evident in both males (O/E 1.10; 95% CI 1.07–1.12) and females (1.08; 1.06–1.10). The co-occurrence of cigarette smoking, alcohol drinking, physical inactivity, and low fruit and vegetable intake was 165% greater in females (2.65; 2.28–3.07) and 110% greater in males (2.10; 1.90–2.32) than expected. Globally, adolescents exhibit multiple modifiable risk factors for future development of NCDs. Early gender-specific prevention strategies targeting clusters of lifestyle risk factors should be prioritised to help mitigate future burden of NCDs globally. Periodical collection of behavioural risk factor data should be encouraged to facilitate a sustainable global surveillance.