Dysregulated cortisol is a risk factor for poor health outcomes. Children of distressed mothers exhibit dysregulated cortisol, yet it is unclear whether maternal distress predicts cortisol activity in later developmental stages. This longitudinal study examined the prospective relation between maternal distress during late childhood (9–12 years) and adolescence (15–19 years) and cortisol response in offspring in young adulthood (24–28 years). Data were collected from 51 recently divorced mothers and their children across 15 years. Higher maternal distress during late childhood was associated with lower total cortisol independent of levels of maternal distress in adolescence or young adulthood. Maternal distress during adolescence marginally predicted blunted cortisol when distress in childhood was low. Findings suggest that blunted cortisol activity in young adulthood may be a long-term consequence of exposure to maternal distress earlier in development.