Adolescents with attention deficit/hyperactivity disorder (ADHD) are at an increased risk for substance use but the pathways through which this risk emerges are insufficiently understood. Tobacco, alcohol, and marijuana outcomes were compared between adolescents diagnosed with ADHD in early childhood (N = 113) and demographically similar controls (N = 65). Participants were assessed from age 5 until age 18. A comprehensive history of adolescent substance use was compiled for each participant and growth in ADHD and conduct disorder (CD) were modeled as they related to substance use outcomes. Results indicated that when compared with controls, adolescents with ADHD were more likely to try cigarettes, initiate alcohol use at early ages, and smoke marijuana more frequently. Furthermore, adolescents with ADHD were 4 to 5 times more likely than controls to escalate to heavy cigarette and marijuana use after trying these substances once. Adolescents with ADHD who escalated to heavy use patterns were more likely to display early cigarette use and marked problems with family members, but displayed fewer peer problems. There was evidence of baseline effects (latent intercept, measured at age 5) for both ADHD and CD on substance use outcomes. Furthermore, growth in ADHD symptoms accounted for much of the growth in CD symptoms, and consequently, escalating CD symptoms in childhood (latent slope) were viewed as a mediator of the relationship between ADHD and cigarette and marijuana use. Maternal drinking in early childhood was the strongest predictor of early adolescent alcohol use. These findings are discussed with respect to the role of ADHD in the development of adolescent risk outcomes.