One specific instantiation of the storm-and-stress view of adolescence is the idea that “normal” adolescence involves high-risk substance use behaviors. However, although uptake of some substance use behaviors is more common during adolescence than other life stages, it is clear that not all adolescents engage in risky substance use—and among those who do, there is much variation in emotional, behavioral, and contextual precursors of this behavior. One such set of predictors forms the internalizing pathway to substance use disorder, whereby internalizing symptoms in childhood such as negative affect and anxiety set off a chain of consequences culminating in high-risk substance use in late adolescence. However, findings linking internalizing symptoms to substance use are mixed, and it is clear that this link varies across adolescents and contexts. One heretofore unanswered question is whether and how geographic location, specifically whether the adolescent lives in an urban or rural location, moderates this link. The current report is a secondary analysis of data from the Longitudinal Study of Australian Children (LSAC; N = 2,285), in which we examined the link between internalizing symptoms in childhood and initiation of substance use through age 19. Using a multiple event process survival mixture model (MEPSUM), we identified three trajectories of substance use initiation in adolescence: one (65.7% of the sample) characterized by near-complete abstinence until late adolescence, another (27.2%) by earlier initiation of alcohol, nicotine, and cannabis, and another (7.2%) by early initiation of these substances and later initiation of more hazardous drugs such as cocaine and methamphetamine. Although childhood externalizing symptoms increased the risk of being in the second or third class, internalizing symptoms decreased risk when rural and non-rural adolescents were considered together. Few effects of rurality were found, but the negative relationship between internalizing at age 10 and high-risk substance use was only observed among non-rural adolescents. This finding, which was inconsistent with our initial predictions that rurality might confer higher risk for substance use, instead suggests a potentially protective effect of internalizing symptoms for engagement in risky substance use which may differ based on an adolescent’s geographical context.