Most adolescents engage in indiscriminate sexual experimentations. This practice exposes them to the risk of contracting sexually transmitted infections including HIV/AIDS. Human immunodeficiency virus (HIV) and acquired immune deficiency syndromes (AIDS) are among the deadly diseases that exist globally. Twice as many girls, compared to boys engage in sexual activity before the age of 15 years (Federal Republic of Nigeria (FRON), (2012). The knowledge of HIV prevention is significantly less among girls aged (15-19 years) compared to boys of the same age range. HIV/AIDS keeps increasing in Nigeria and fewer schools provide life skills-based HIV/AIDS education. Schools are considered the primary centers for impartation and acquisition of knowledge and skills. This study investigated the sexual behavior of female secondary school adolescents and school-based HIV/AIDS education. Descriptive survey was the data collection method used. Female secondary school students (n = 2010) completed the questionnaire forms on sexual behavior. Teachers (n = 50) participated in in-depth interviews on school based HIV/AIDS education. Quantitative data were analyzed with descriptive statistics. Qualitative data were transcribed and analyzed. Validity of the qualitative data was established through the use of member checks. One thousand five hundred and seventy-two participants were sexually active (78.5%). Four hundred and thirty participants never had sexual intercourse (21.5%). Sexually active adolescents who used preventive measures of different types totaled 911(58.0%). Six hundred and sixty one participants (42.0%) did not use any preventive measure. Findings revealed sexually active participants were at increased risk of HIV/AIDS infections. In-depth interviews determined no significant HIV/ AIDS education in the schools. A high number of sexually active adolescents suggests the need for more intervention programs on life skills-based HIV/AIDS and sexuality education.