Family affluence plays a crucial role in adolescent well-being and is potential source of health inequalities. There are scarce research findings in this area from a cross-national perspective. This study introduces several methods for measuring family affluence inequality in adolescent life satisfaction (LS) and assesses its relationship with macro-level indices. The data (N = 192,718) were collected in 2013/2014 in 39 European countries, Canada, and Israel, according to the methodology of the cross-national Health Behavior in School-aged Children study. The 11-, 13- and 15-year olds were surveyed by means of self-report anonymous questionnaires. Fifteen methods controlling for confounders were tested to measure social inequality in adolescent LS. In each country, all measures indicated that adolescent from more affluent families showed higher satisfaction with their life than did those from less affluent families. According to the Poisson regression estimations, for instance, the lowest inequality in LS was found among adolescents in Malta, while the highest inequality in LS was found among adolescents in Hungary. The ratio between the mean values of LS score at the extreme highest and lowest family affluence levels (Relative Index of Inequality) derived from the regression-based models distinguished for its positive correlation with the Gini index, and negative correlation with Gross National Income, Human Development Index and the mean Overall Life Satisfaction score. The measure allows in-depth exploration of the interplay between individual and macro-socioeconomic factors affecting adolescent well-being from a cross-national perspective.