The relationship between a range of prenatal and perinatal events and risk for psychopathology in offspring was examined. Prenatal and perinatal events investigated included maternal experiences, health, and substance use during pregnancy, obstetric complications, feeding practices, and infant health during the first year of life. Offspring diagnosis was based on structured interviews conducted with 579 adolescents on two occasions. Risk for later psychopathology was associated with a number of prenatal and perinatal factors. Major depression was associated with not being breast fed and maternal emotional problems during the pregnancy. Anxiety was chiefly associated with fever and illness during the first year of life and maternal history of miscarriage and stillbirth. Disruptive behavior disorder was associated with poor maternal emotional health during the pregnancy and birth complications. Risk for substance use disorder was associated with maternal use of substances during the pregnancy. Mediating effects of maternal depression, maternal–child conflict, and physical symptoms in the child, and moderating effects of gender of child and parental education were also evaluated. The limitations of this study are discussed and future research directions are suggested.