Despite an accumulated body of research evidence that documents the negative physical consequences of chronic alcohol and drug use, it is less clear whether the use of these same substances produces impaired cognitive abilities during the early stages of use. Early drug use may impede acquisition of critical thinking skills and hinder the learning of important cognitive strategies required for successful transition to adulthood. To better understand these relations, longitudinal latent-variable analyses were used to examine the effects of early adolescent drug use on early-late adolescent cognitive efficacy. Latent factors of polydrug use, behavioral control, and cognitive efficacy were hypothesized in early adolescence, the latter two controlling for potential spurious relations. At outcome, six constructs were hypothesized tapping polydrug use, cognitive mastery, self-reinforcement, problem-solving confidence, decision-making skills, and cognitive and affective self-management strategies. Models were psychometrically sound and accounted for large portions of variance. Early adolescent drug use had a small but significant negative effect on cognitive and affective self-management strategies. By the 12th grade, linkages between drug use and cognitive functioning were of larger magnitude than long-term influences, perhaps reinforcing the argument that deficits in cognitive skills are developmentally delayed and surface only with exacerbated or persistent drug use. Overall, specific effects of drug use adversely influenced important cognitive skills that may be critically related to functioning in both interpersonal and intrapersonal domains.