Although previous research established a positive association between perceived social support and adolescent life satisfaction, little is known about the relative importance of different sources of support for adolescent life satisfaction and cross-country variations in this respect. Using large-scale representative samples from the 2017/18 Health Behaviour in School-aged Children (HBSC) study, this study examined to what extent the association between social support and life satisfaction in early adolescence varied across different social sources and countries. Also, it examined whether cross-country variations are explained by national-level generalized trust, a sociocultural factor that shapes adolescent socialization. National-level data were linked to data from 183,918 early adolescents (M-age = 13.56, SD = 1.63, 52% girls) from 42 European and North American countries/regions obtained from HBSC. Multilevel regression analyses yielded a positive association between support from different sources and life satisfaction. The strongest associations were found for support from families, followed by teachers and classmates, and weakest for support from friends. Associations varied across different countries/regions. National-level trust amplified the association between perceived classmate support and adolescent life satisfaction. The revealed cross-country differences open avenues for future cross-cultural research on explanations for cross-cultural differences in the association between social support from different sources and life satisfaction in early adolescence.