Psychopathology during adolescence has been associated with poor academic performance, low social well-being, and low social preference by peers at school. However, previous research has not accounted for comorbid psychopathology, informant-specific associations between psychopathology and functioning, and gender and age differences. This study addresses these limitations by examining adolescents' psychopathology and functioning at school, reported by child, parent, teacher, and peers during primary and secondary school in a large Dutch longitudinal cohort study (N = 2230). Teacher reports of psychopathology, especially regarding attention problems and withdrawn/depressed problems, followed by parent reports regarding hyperactivity, were most strongly associated with academic performance. The same held for social preference which was associated with teacher and parent ratings of withdrawn/depressed problems and hyperactivity. In contrast, social well-being was best predicted by child reports (at primary school) of affective problems. In girls, the association between ADHD problems and poor academic performance was stronger than in boys and conduct problems were more often associated with poor school functioning in general. These findings can help identify adolescents at risk for poor functioning and design interventions that effectively reduce or prevent poor school functioning.