Left or mixed-handedness, footedness, and eye dominance are thought to indicate abnormalities in lateralization related to schizophrenia. Increased left or mixed-dominance in schizophrenia suggests possible hemispheric abnormalities associated with the disorder. A related body of research suggests that some indications of lateralization abnormalities may be evident prior to the onset of schizophrenia, suggesting that disruptions in lateralization are inherent to the developmental course of the disorder. We attempted to replicate and extend upon findings indicating differences in lateralization between children who later developed a schizophrenia spectrum disorder (n = 26) and those who did not develop a schizophrenia spectrum disorder (n = 216), among a high-risk and control, longitudinal sample. The rate of left or mixed-footedness, eye dominance, and any anomalous lateralization, but not handedness, discriminated between those who developed schizophrenia spectrum disorders and those who did not. Left or mixed-laterality appears to signal neurological disruption relevant to the development of schizophrenia spectrum disorders.