Adolescents spend substantial time learning and socializing at school. Peer victimization (a negative peer relationship) and teacher unfairness (a negative student--teacher relationship), which are commonly embedded within the school environment, could exert negative effects on adolescent life satisfaction (ALS). Although an emerging line of research has revealed the independent effects of peer victimization and teacher unfairness on ALS, scant research has analyzed how peer victimization and teacher unfairness could influence ALS using nationally representative data. A sample of 5712 15-year-old adolescents from the USA who participated in the 2015 program for international student assessment was used in the present study. The results of structural equation modeling showed that both peer victimization and teacher unfairness had significant and negative effects on ALS; sense of belonging to school partially mediated the effect of peer victimization on ALS, and schoolwork-related anxiety partially mediated the effects of both peer victimization and teacher unfairness on ALS. The research findings extended our understanding of the mechanisms underlying peer victimization, teacher unfairness, and ALS.