The long-term clinical and functional outcomes of preschool-age irritability are unknown. This study examined longitudinal associations of preschool irritability with psychiatric disorders and functional impairment in adolescence in a large community sample. 453 children were assessed at age three and at ages 12 and/or 15. At age three, parents were interviewed about their child’s irritability, psychiatric symptoms, and impairment. In adolescence, parents and youth were interviewed to assess youth psychopathology, depressive and anxiety symptoms, and impairment. Irritability at age three predicted internalizing and externalizing disorders in adolescence, parent-reported anxiety and depressive symptoms, and greater functional impairment, including poorer peer functioning, physical health, and antidepressant and educational service use, even after controlling for baseline psychiatric disorders. All longitudinal associations persisted after further adjusting for well-established early life risk markers for psychopathology. Findings underscore the clinical significance and predictive power of preschool irritability and provide support for its use in intervention efforts.