BACKGROUND: Loneliness is an intense psychosocial health problem among adolescents. This study was carried out to comprehensively examine the prevalence and risk factors associated with loneliness among adolescents. METHODS: We analyzed data from a comprehensive survey Global School-based Student Health Survey (GSHS) involving 179,937 adolescents aged 11-17 years from 59 countries. Binary logistic regression was applied to identify the factors associated with loneliness among adolescents. RESULTS: A total of 179,937 adolescents aged 11-17 years from 59 countries where 85,158 (47.44 %) male and 94,362 (52.56 %) female participated in the study. Eastern Mediterranean Region had the greatest prevalence (15.83, CI: 15.81-15.84), much higher than the overall prevalence of 11.16. In contrast, South-East Asia had the lowest estimate (8.45, CI: 8.44-8.58), indicating better results or lower prevalence. The African Region (12.21, CI: 12.19-12.23) and Region of the Americas (11.01, CI: 10.98-11.04) are closer to the world average than the Western Pacific Region (10.50, 10.48-10.52). Occasionally, adolescents experienced food insecurity (AOR: 1.21, 95 % CI: 1.1-1.33) and frequently or always (AOR: 2.11, 95 % CI: 1.81-2.46) had high levels of loneliness. Being bullied, physically fighting, seriously injured, had no close friends, parents sometimes or rarely check homework, parents never understand problem, sedentary behavior 3-4 h or >
4 h, suicidal ideation, and suicidal plan were all highly associated with loneliness. CONCLUSION: This study highlights the pressing need for policies and programs aimed at mitigating the mental health crisis among adolescents globally.