Previous research has shown that educational attainment is a protective factor for substance use and sexual risk among adolescents and young adults. Evidence also shows that this relationship may differ by race/ethnicity and gender. This study aimed to elucidate the relationship between educational attainment, substance use, and sexual risk among African American women in emerging adulthood. This study uses cross-sectional data from 646 African American women (aged 18 to 25) enrolled in a randomized trial of a behavioral HIV risk-reduction intervention. At enrollment, participants completed a risk behavior assessment via audio-computer assisted self-interview and provided a urine sample for drug screening. Bivariate logistic regression analyses were conducted to examine substance use and sexual risk factors associated with educational attainment: completing some college or more as compared with completing high school or less. Participants who completed some college or more (52%) were more likely to report heavy alcohol use (four or more drinks in one day) in the past 30 days (OR = 1.48; p = 0.014) and more likely to report alcohol or other drug use just before or during last sex (OR = 1.43; p = 0.026) compared with participants who completed high school or less. Completing some college or more was protective for having a positive urine screen for cocaine (OR = 0.43; p = 0.018) and reporting condomless sex at last sex (OR = 0.71; p = 0.041). Differences in positive marijuana screens, reporting a previous STI, or reporting their partner used alcohol or other drugs at last sex were not statistically significant. The findings reveal notable differences in the magnitude and direction of associations between educational attainment and substance use and sexual risk. Although educational attainment is subject to change because of the frequent pursuit of education during emerging adulthood, the findings may have important implications for tailoring HIV risk-reduction interventions to key populations, such as African American women.