Health equity research has identified fundamental social causes of health, many of which disproportionately affect Black Americans, such as early life socioeconomic conditions, neighborhood disadvantage, and racial discrimination. However, the role of life course factors in premature mortality among Black Americans has not been tested extensively in prospective samples into later adulthood. To better understand how social factors at various life stages impact mortality, this study examines the effect of life course poverty, neighborhood disadvantage, and discrimination on mortality and factors that may buffer their effect (i.e., education, social integration) among the Woodlawn cohort (N = 1242), a community cohort of urban Black Americans followed since 1966. Taking a life course perspective, we analyze mortality data for deaths through age 58 years old, as well as data collected at ages 6, 16, 32, and 42. At age 58, 204 (16.4%) of the original cohort have died, with ages of death ranging from 9 to 58.98 (mean = 42.9). Cox proportional hazard models adjusting for confounders show statistically significant differences in mortality risk based on timing and persistence of poverty; those who were never poor or poor only in early life had lower mortality risk at ages 43-58 than those who were persistently poor from childhood to adulthood. Education beyond high school and high social integration were shown to reduce the risk of mortality more for those who did not experience poverty early in their life course. Findings have implications for the timing and content of mortality prevention efforts that span the full life course.