This study conducted to investigate factors associated with early sexual debut and related HIV/AIDS knowledge among female adolescents. A simple random sampling was performed to obtain 120 girls from one study district and three wards. The respondents included school-going and non-school-going young girls in the study area. Using mixed research method, this study employed a follow-up explanatory model, which allowed the use of qualitative data to explain and expound the quantitative findings. Data were collected using cross-sectional survey and interview. Chi square tests were run to assess the association between socio-demographic factors and early sexual debut among female adolescents in Mtwara District. Descriptive statistics and content analyses were employed to describe the respondents’ awareness and knowledge level of HIV/AIDS and the impacts of early sexual debut. Results in this study indicated that 70 percent of the respondents had their sexual debut as minors, whereas 30 percent had not involved themselves in sexual intercourse. Results also showed that age (χ 2 =11.315, df=1, sign=0.001), peer pressure (χ 2 =65.013, df=1, sign=.000) and family members living with the respondents (χ 2 =8.832, df=3, sign=0.032 were significantly associated with young female adolescents’ engagement in early sexual intercourse. Majority (69.2%) of the female adolescents were informed of the HIV/AIDS dynamics. Knowledge level was found to be significantly associated with engagement in early sexual debut (χ 2 =11.613, df=1, P=0.001). This study also showed that, 36.9 percent of young girls experienced poor academic performance, teenage pregnancy (13.1%), early marriage (8.3%), and school dropout (19%) due to their early initiation into sexual relations. Therefore, the study argues that female adolescents in Mtwara District were reported to begin sexual debut much early and some of them had little knowledge on how they should protect against HIV transmission. Hence, study argues the importance of both (father and mother) parenting system that it may help to shape adolescents’ sexual behaviour.Mtwara District council