Sub-Saharan Africa is a region that is severely affected by the HIV and AIDS pandemic with females disproportionately affected. Having accurate and comprehensive knowledge about HIV and AIDS is a major strategy in the fight against the pandemic. This study sought to examine the individual and contextual predictors of comprehensive HIV and AIDS knowledge among young women in Ghana. The study used the females’ file from the 2014 Ghana Demographic and Health Survey dataset. A total of 1 407 young women were used for the analysis. Both bivariate and multivariate analyses were done. The results showed that about 22% of the respondents had comprehensive HIV and AIDS knowledge. Young women with secondary and higher levels of education (AOR = 2.85, p < 0.01) and those from the Upper East Region (AOR = 7.15, p < 0.001) had higher odds of comprehensive HIV and AIDS knowledge. However, those cohabiting (AOR = 0.57, p < 0.01) and those who do not watch TV at all (AOR = 0.50, p < 0.01) had lower odds of comprehensive HIV and AIDS knowledge. Comprehensive HIV and AIDS knowledge is low among young women in Ghana and the predictors are both individual (marital status and education) and contextual (region, watching television and listening to radio). A concerted effort is needed to improve the HIV and AIDS knowledge of young people. Mass media campaigns aimed at improving comprehensive HIV and AIDS knowledge should appreciate the individual and contextual factors that influence the comprehensive HIV & AIDS knowledge of young women.