Of 901 rural learners (X age 16.1, SD = 2.4) at 10 randomly selected high schools in KwaZulu-Natal, South Africa, those living with a parent were less likely to drink alcohol (P < 0.0001) or use drugs (P = 0.006). Thirty percent (95% CI 26.9, 33.1) were sexually active, and 53.1% used a condom in the past 30 days. The odds of males being sexually active was 7.27 the likelihood of females (95% CI 5.2, 10.1). Only one-third of male respondents always used condoms. Of sexually active respondents, 46.5% had experienced coercive sex. More males (14.1%) than females (3.6%) smoked cigarettes (P < 0.0001). The odds of males drinking alcohol was 4.5 times that of females (P < 0.0001). Smoking, (OR 2.42, 95% CI 1.32, 4.44) and drinking, (OR 2.67, 95% CI 1.71, 4.19) among learners increased the likelihood of sexual activity. With youth at increasing risk of HIV/AIDS in KwaZulu-Natal, South Africa, interventions to reduce learners' risk behaviors are required.