A long-standing and diverse body of evidence has documented the importance of externalizing characteristics as very early etiologic predictors of a pathway to severe alcohol and other drug problems and substance use disorder. At the same time, much remains unclear about the mechanistic structure of this pathway, including understanding what the defining characteristics are that encompass the diverse behaviors included in the externalizing domain. This article proposes that the core risk phenotype unifying this domain is behavioral undercontrol/disinhibition. It describes the defining features of this phenotype and outlines the mediators, moderators, and developmental course that characterize the pathway from early risk to a substance use disorder endpoint. A brief summary of the neurocognitive and brain functional response systems that underlie the behavioral phenotype emphasizes the operation of two systems in dynamic tension, one an effortful control system, the other an incentive reactivity system.