Environmental context is an important predictor of health behavior. Understanding its effect on cannabis use among pregnant women is yet to be understood. The aim of the study is to assess the impact of perceived neighborhood environment on prenatal cannabis use and explore the mediating role of stress. Data are from the Life-Course Influences on Fetal Environments Study (LIFE), a retrospective cohort of postpartum African American women in Metropolitan Detroit, Michigan (2009-2011). Prenatal cannabis use was defined as self-reported ever use during pregnancy. Three perceived neighborhood scales were considered: social cohesion and trust, social disorder, and danger and safety. Out of 1,369 women, 151 (11.0%) self-reported using cannabis during pregnancy. After adjusting for age, marital status, income, years of education, and general social support scale, the odds of cannabis use significantly increased among the lowest quartiles of all the neighborhood scales suggesting higher cannabis use among women who perceived their neighborhoods to have the worst conditions. Compared to the highest quartile, the odds ratio (OR) for the lowest quartiles for social cohesion and trust, social disorder, and danger and safety were 1.77 (95% confidence interval (CI): 1.04-3.03), 1.83 (95% CI: 1.15-2.91), and 1.93 (95% CI: 1.12-3.31) respectively. Evidence of mediation by perceived stress was only present between the association of perceived levels of safety and danger with cannabis use during pregnancy. Future prospective studies are warranted to understand the causal associations between individual correlates and social and physical environmental factors of prenatal cannabis use.