Although previous research has documented the adverse influence of early socioeconomic disadvantage on youths’ physical health outcomes and the increase in health inequalities over the early life course, little is known about genetically informed sequential life course developmental processes leading to health outcomes. Consistent with the life course-stress process perspective, we hypothesized that early socioeconomic adversity initiates a stress process over the early life course. This process involves the disrupted transition from adolescence to young adulthood, which increases the risk of health problems during young adulthood. Behavioral, psychosocial, and genetic data were collected from 12,424 adolescents (53 % female) over a period of 13 years participating in the nationally representative National Longitudinal Study of Adolescent Health (Add Health). Early cumulative socioeconomic adversity and the polygenic influence were measured using composite indices. The study provided evidence for stressful developmental processes of adolescents, involving parental rejection, depressive symptoms, and adolescents’ precocious transition. This longitudinal process was initiated by early cumulative socioeconomic adversity and eventuated with young adults’ increased body mass index (BMI). Furthermore, the study provided evidence for the influence of life context–gene interactions (G × E) on adolescents’ precocious development and young adult BMI (after controlling for the lagged measure) amplifying the stress process over the early life course. These findings emphasize the need for incorporating individual genetic characteristics in a longitudinal context into life course stress research. Furthermore, policies focused on eradicating childhood/adolescent adversities are necessary as well as youth programs and policies that promote youth competencies that aid in their successful transition to young adulthood.