African American women are 10.8 times more likely to be diagnosed with HIV compared with White women. This descriptive study fills a gap by examining associations among social and contextual factors and sexual communication, condom use, and safer sex negotiation among African American women. Study participants between 18 and 25 years of age and who reported recent substance use were recruited from three North Carolina counties. A risk behavior survey was administered via audio computer-assisted self-interview, and logistic regression analyses were conducted to assess associations between social and contextual variables and condom use at last sex with a main partner. Education (AOR: 2.078; 95% CI: 1.214, 3.556), sexual communication with a main partner (AOR: 1.079; 95% CI: 1.050, 1.109), and condom use relationship scale (AOR: 1.059; 95% CI: 1.023, 1.098) were positively associated with condom use at last sex, whereas living with a main partner (AOR: 0.447; 95% CI: 0.210, 0.950) and the alcohol and drug problem scale (AOR: 0.971; 95% CI: 0.944, 0.998) were negatively associated with condom use (p < 0.05). The study findings show that among young African American women at risk for HIV, contextual and personal factors may influence condom use. A socio-ecological approach combining personal empowerment, interpersonal, structural, and biobehavioral strategies is necessary in implementing holistic gender-focused HIV prevention programs.