Little is known about the mediating role of adolescent chronic pain in the connection between adolescent parental rejection and psychosocial and physical health (i.e., disease risk) outcomes in young adulthood (YA). To address this gap, the present study tested a model of a successively contingent developmental process that integrates neurophysiological research and the life course developmental perspective. The model included parental rejection and chronic pain in adolescence and depressive symptoms, low education attainment, economic hardship and allostatic load in YA. The study utilized 13 years of prospective data from a nationally representative sample of 11,030 US adolescents. The findings largely supported the hypothesized model. Adolescent chronic pain, as influenced by parental rejection, was associated with depressive symptoms and economic hardship in YA. In addition, parental rejection directly influenced depressive symptoms, education level and economic hardship, all of which, in turn, contributed to greater physical health risk (i.e., allostatic load) in YA. These associations persisted even after controlling for adolescent illness, depressive symptoms, age, sex and race/ethnicity. Multi-group analysis showed that female participants were more vulnerable to stressful parental rejection and socioeconomic difficulties in YA. The theoretical and practical implications of these findings are discussed.