This cross-sectional study assessed sexually transmitted infection (STI) prevalence, socio-demographic characteristics, substance use, sexual behaviors, and sexual network profiles among African American sexual minorities in Jackson, Mississippi. Bivariate chi-square tests and generalized estimating equation (GEE) models explored individual and partner-related factors. Compared to their heterosexual counterparts, male African American sexual minorities reported fewer sex partners (odds ratios [OR] 0.33, 95% confidence intervals [CI] 0.16-0.65) and lower concurrency levels (OR 0.42, 95%CI 0.24-0.72). African American sexual minority women reported greater substance abuse, more sex partners (OR 2.54, 95%CI 1.47-4.38), higher concurrency levels (OR 1.81, 95%CI 1.24-2.64), and more transactional sex (OR 2.52, 95%CI 1.25-5.11). These results highlight the need for nuanced STI interventions tailored to African American sexual minorities in Mississippi.