Children differ in their general temperament and these differences predict consequential outcomes, including mental health, peer relations, and academic performance. In adults, there is strong evidence that personality correlates with substance use, but the temporal direction of the relation is unclear, as substance use may alter personality. The present research uses data from the Longitudinal Study of Australian Children (N = 5,362) to examine whether temperament assessed by parents in early childhood is associated with adolescent self-reported initiation of alcohol, cigarette, marijuana, or other drug use. Children rated higher on sociability at 4-5 years old were at higher risk of initiation for all types of substances in adolescence (age 12 to 17), controlling for SES, single-parent household, parent substance use, and other demographic variables. Additionally, children rated higher on reactivity were at higher risk of cigarette or marijuana use initiation, and children rated higher on persistence had a lower risk of cigarette use initiation. This multi-informant prospective study demonstrates that early individual differences in psychological functioning predict risk of future substance use initiation and highlights the importance of considering temperament and personality when assessing risk of future substance use initiation.