While appropriate hand hygiene practices (HHP) are protective against infections, the paucity of evidence on global estimates and determinants of HHP in adolescents limits effective design and planning of intervention to improve HHP in young people. We examined the prevalence and correlates of HHP in adolescents. We used nationally representative data from the Global School-based Student Health Survey (2003–2017) from 92 countries. HHP were categorized as “appropriate”, “inappropriate” and “lacking” based on the information about “hand washing before eating”, “hand washing after using the toilet”, and “hand washing with soap”. Multinomial logistic regression analyses were used to assess the role of socio-demographic, health, lifestyle, school, and family-related variables in HHP. Among 354,422 adolescents (13–17 years), only 30.3% were found to practice appropriate hand hygiene. Multivariable models suggest that sedentary behavior (adjusted relative risk ratio (ARRR) 1.41, 95% CI 1.31–1.51)), and bullying victimization (ARRR 1.20, 95% CI 1.10–1.30) promoted inappropriate HHP. In contrast, parental supervision (ARRR 0.55, 95% CI 0.50–0.59) and parental bonding (ARRR 0.81, 95% CI 0.75–0.87) were protective against inappropriate HHP. From a policy perspective, hand hygiene promotion policies and programs should focus on both school (bullying, exercise) and family-level factors (parental supervision and parental bonding) factors.