Scores of intervention programs these days apply instructional and, sometimes, systemic strategies to reduce bullying in schools. However, meta-analyses show that, on average, such programs decrease bullying and victimization only by around 20%, and often show no or negative effects in middle and high schools. Due to these sobering results, we propose the idea that bullying prevention for adolescents needs to focus more strongly on systemically informed relationship-building efforts. Building on past research, this study focuses on several aspects of relationships and classroom climate which are significant predictors of bullying behaviors: SES, ethnicity, and teaching quality. We propose the hypothesis that the link between classroom-level bullying and three classroom-level factors-students' SES background, students' ethnicity, and teaching quality-is mediated by the quality of student-teacher and student-student relationships (STR and SSR). The study uses multilevel structural regression modeling (M-SRM) to analyze a large and ethnically diverse American survey dataset (N = 146,044 students). Results confirm the hypothesis, showing that the relationships between SES and bullying, and between ethnicity and bullying, are entirely mediated by the quality of STR and SSR; the link between SES and bullying is even over-explained by the two relationship factors. Furthermore, the quality of STR is a positive predictor of medium strength (standardized coefficient = 0.45) of the quality of SSR. The findings suggest that schools with high levels of bullying behavior among students need to (re-)focus teacher professional development on relationship-building skills as well as instructional and a range of systemically informed improvement efforts.