The ways adolescents develop and use strategies to cope with stress vary according to cultural scripts and values. This cross-sectional study tested the impact of region and gender on adolescents' stress perceptions and coping styles. A total sample of 10,941 adolescents (51.3% female) from 20 countries completed questionnaires on stress and coping behaviors in four domains (school, parents, peers, and romantic relationships). Standardized samples of n = 200 were drawn from each country, resulting in a sample of N = 4,000 adolescents (mean age 15.18, SD = 1.76, balanced gender distribution). Based on the results of discriminant analysis, the adolescents could be grouped into three world regions (Western, Eastern/Asian, and Southern). Results revealed that levels of perceived stressfulness of issues in different domains were universally similar among adolescents from all three regions. Parent- and school-related stress received the highest rankings, and peer- and romance-related stress the lowest. Differences emerged with respect to coping style, depending on region and gender. Coping styles characterized by negotiating, seeking support, and emotional outlet were used more often by adolescents from the Western region than those from the Eastern/Asian or Southern regions. Females in all regions had higher rates in the use of negotiating and seeking support than males did. Adolescents from all countries, despite regional variations, exhibited more emotional outlet in response to conflicts with parents than with peers or romantic partners. Overall, adolescents from all regions of the world demonstrated an impressive level of coping competencies, as only about one fifth of all coping responses involved the use of withdrawal and denial. The findings are discussed with respect to how the effects of globalization and changing societal expectations may have contributed to similar levels of perceived stressfulness and increased coping agency in adolescents in different parts of the world.