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Abstract ObjectivesThe COVID‐19 pandemic in South Africa introduced new societal adversities and mental health threats in a country where one in three individuals are expected to develop a psychiatric condition sometime in their life. Scientists have suggested that psychosocial stress and trauma during childhood may increase one's vulnerability to the mental health consequences of future stressors—a process known as stress sensitization. This prospective analysis assessed whether childhood adversity experienced among South African children across the first 18 years of life, coinciding with the post‐apartheid transition, exacerbates the mental health impacts of psychosocial stress experienced during the 2019 coronavirus (COVID‐19) pandemic (ca. 2020–2021). Materials and MethodsData came from 88 adults who participated in a follow‐up study of a longitudinal birth cohort study in Soweto, South Africa. Childhood adversity and COVID‐19 psychosocial stress were assessed as primary predictors of adult PTSD risk, and an interaction term between childhood adversity and COVID‐19 stress was calculated to evaluate the potential effect of stress sensitization. ResultsFifty‐six percent of adults exhibited moderate‐to‐severe PTSD symptoms. Greater childhood adversity and higher COVID‐19 psychosocial stress independently predicted worse post‐traumatic stress disorder symptoms in adults. Adults who reported greater childhood adversity exhibited non‐significantly worse PTSD symptoms from COVID‐19 psychosocial stress. DiscussionThese results highlight the deleterious mental health effects of both childhood trauma and COVID‐19 psychosocial stress in our sample and emphasize the need for greater and more accessible mental health support as the pandemic progresses in South Africa.