The effects of prenatal marijuana and alcohol exposure on school achievement at 10 years of age were examined. Women were interviewed about their substance use at the end of each trimester of pregnancy, at 8 and 18 months, and at 3, 6, 10, 14, and 16 years. The women were of lower socioeconomic status, high-school-educated, and light-to-moderate users of marijuana and alcohol. The sample was equally divided between Caucasian and African-American women. At the 10-year follow-up, the effects of prenatal exposure to marijuana or alcohol on the academic performance of 606 children were assessed. Exposure to one or more marijuana joints per day during the first trimester predicted deficits in Wide Range Achievement Test-Revised (WRAT-R) reading and spelling scores and a lower rating on the teachers' evaluations of the children's performance. This relation was mediated by the effects of first-trimester marijuana exposure on the children's depression and anxiety symptoms. Second-trimester marijuana use was significantly associated with reading comprehension and underachievement. Exposure to alcohol during the first and second trimesters of pregnancy predicted poorer teachers' ratings of overall school performance. Second-trimester binge drinking predicted lower reading scores. There was no interaction between prenatal marijuana and alcohol exposure. Each was an independent predictor of academic performance.