The temperamental trait of negative emotionality (NE) plays an important role in maladaptation among adults experiencing significant life stress. However, the prospective relation between childhood NE and subsequent interrelated behavioral, emotional, and biological dysregulation in later life has not yet been established among children who experience early adversity. Using a longitudinal sample of youth who experienced parental divorce during childhood (N = 160; 53% male; 83% White), we tested the hypothesis that childhood NE would predict physiological, emotional, and behavioral dysregulation 15 years later. NE was assessed by maternal report when youth were between 9 and 12 years old. Fifteen years later, young adults (mean age = 25.55 years) participated in a psychosocial stress task to assess cortisol reactivity and reported on internalizing symptoms and problematic alcohol use. Structural equation modeling revealed that higher childhood NE predicted significantly greater alcohol use, internalizing symptoms, and total cortisol output during a stress task 15 years later. Importantly, these findings held after adjusting for childhood internalizing symptoms. In addition, problematic alcohol use was associated with greater cortisol reactivity and internalizing symptoms. Findings suggest that childhood NE is a critical risk marker for interrelated forms of dysregulation in young adulthood among at-risk youth.