This study aims to test whether adolescent negative social interactions mediate the relation between early adolescent self-regulatory capacities and young adult psychopathology, using a fully prospective mediation model. Data were derived from the Tracking Adolescents’ Individual Lives Survey, a large population cohort of Dutch adolescents (n = 962). At age 11, three indicators of self-regulation were assessed: low frustration, high effortful control, and high response inhibition. Negative social interactions between ages 11 and 22 were captured twice using the Event History Calendar. Psychopathology (i.e., internalizing and externalizing problems) was assessed at ages 11 and 22. Findings indicate that adolescents’ frustration and effortful control but not response inhibition assessed at age 11 are related to both internalizing and externalizing problems at age 22, after controlling for psychopathology at age 11, sex, and socioeconomic status. These associations were partly (about 22%) mediated by the negative social interactions adolescents experienced. Effect sizes were all modest. This study shows that self-regulation is related to subsequent psychopathology in part through its effect on negative social interactions, providing evidence for sequences of self-regulatory capacities, life experiences, and developmental outcomes.