The goal of the current investigation was to test emotion dysregulation as a mechanism explaining the longitudinal association between peer rejection and depressive symptoms across 1 school year in middle childhood and to determine whether this process differed based on gender and grade. Youth in Grades 3 through 6 (N = 131; 71 girls) and their primary school teachers (n = 8) were recruited from a Midwestern elementary school. Youth reported on their emotion dysregulation and depressive symptoms at two time points (T1 and T2), approximately 6 months apart. Teachers completed ratings of peer rejection at T1. Peer rejection at T1 predicted youth-report of depressive symptoms at T2, even after controlling for depression at T1. Moderated mediation suggested that change in emotion dysregulation mediated the relation of peer rejection to depressive symptoms over time, but only for older boys. Results underscore the importance of considering gender-specific processes within interpersonal risk models of depression, and provide support for peer rejection as a critical social process shaping emotion regulation in middle childhood.