BACKGROUND: Adversities operating over intrauterine life have been associated with risk of schizophrenia, but the biology of resultant developmental perturbation is poorly understood. AIMS: To examine the relationship of congenital anomalies and related functional impairments in infancy to risk of schizophrenia. METHOD: Using the Congenital Anomalies data-set from the Prenatal Determinants of Schizophrenia birth cohort, congenital anomalies and related functional impairments were categorised and related to subsequent risk of schizophrenia-spectrum disorder. RESULTS: The presence of any hypothesis-based congenital anomaly or related functional impairment was associated with a doubling of risk of schizophrenia-spectrum disorder. In contrast, having any other congenital anomaly or related functional impairment was not associated with risk of schizophrenia-spectrum disorder. CONCLUSIONS: These findings constitute evidence for early events, which may result from both genetic predisposition and environmental insults, in the pathogenesis of schizophrenia.