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Research showing that risk for schizophrenia, bipolar disorder with psychosis, and other psychosis-spectrum diagnoses in adulthood is multidetermined has underscored the necessity of studying the additive and interactive factors in childhood that precede and predict future disorders. In this study, risk for the development of psychosis-spectrum disorders was examined in a 2-generation, 30-year prospective longitudinal study of 3,905 urban families against a sociocultural backdrop of changing economic and social conditions. Peer nominations of aggression, withdrawal, and likeability and national census information on neighborhood-level socioeconomic disadvantage in childhood, as well as changes in neighborhood socioeconomic conditions over the lifespan, were examined as predictors of diagnoses of schizophrenia, bipolar disorder, and other psychosis-spectrum disorders in adulthood relative to developing only nonpsychotic disorders or no psychiatric disorders. Individuals who were both highly aggressive and highly withdrawn were at greater risk for other psychosis-spectrum diagnoses when they experienced greater neighborhood disadvantage in childhood or worsening neighborhood conditions over maturation. Males who were highly aggressive but low on withdrawal were at greater risk for schizophrenia diagnoses. Childhood neighborhood disadvantage predicted both schizophrenia and bipolar diagnoses, regardless of childhood social behavior. Results provided strong support for multiple-domain models of psychopathology, and suggest that universal preventive interventions and social policies aimed at improving neighborhood conditions may be particularly important for decreasing the prevalence of psychosis-spectrum diagnoses in the future.