To date, studies on psychosocial determinants of condom use among adolescents in Africa have mainly focused on more literate urban youth. In this study, we investigated the psychosocial determinants of condom use among low-literate females in rural Ethiopia. Moreover, some controversy exists on the role of perceived vulnerability to HIV infection to promote HIV preventive behavior in Africa, which we also tried to clarify in this study. In this study, 200 rural females participated, aged 13–24, from the Amhara Highland in Ethiopia. Using data collectors who interviewed the low-literate females with a structured questionnaire, we assessed perceived vulnerability to HIV infection, response efficacy of condom use, self-efficacy, attitude to condom use, and subjective norm to condom use. Moreover, we assessed intended and actual condom use. Compared to non-users of condoms, users of condoms scored significantly higher on all psychosocial determinants. Regression analysis indicated that vulnerability, condom attitude, and self-efficacy were significantly related to intended condom use. Attitude, vulnerability, and response-efficacy were significantly related to actual condom use. Among low-literate females in rural Ethiopia, psychosocial determinants were strongly related to intended and actual condom use, which indicates the usability of psychosocial models of condom use among low-literate females.