HIV/AIDS has been a major threat to global public health, with India ranking third when it comes to the global burden of people living with HIV, especially women. It is imperative to assess the level of knowledge women have about transmission and prevention of this infection. This study sought to delineate the determinants of the comprehensive knowledge of HIV/AIDS among women in the reproductive age groups in India. Data from the fifth round of the National Family Health Survey conducted in India were analyzed. The sample included 95,541 women aged 15–49 years. Multilevel logistic regression was fitted with individual characteristics, household characteristics, and community characteristics to identify determinants of comprehensive knowledge on HIV/AIDS. Nearly a fourth (24.8%) of the women aged 15–49 in India who had ever heard of HIV had comprehensive knowledge of HIV/AIDS. Multilevel logistic regression showed that the likelihood of comprehensive knowledge of HIV/AIDS was higher among women aged 40–44 (AOR = 1.57) and 30–34 (AOR = 1.56). The likelihood of having comprehensive knowledge increased with the increase in the level of education. Women with secondary and higher levels of education were 1.9 times and 3.38 times more likely to have comprehensive knowledge, respectively, than those with no education. Household wealth, access to mass media, and having ever tested for HIV were also significant determinants of comprehensive knowledge of HIV/AIDS among women. The odds of having comprehensive knowledge about HIV/AIDS were higher for women with higher community wealth (AOR = 1.31), higher community education (AOR = 1.09), and higher community employment (AOR = 1.12). Factors at both the individual and community levels were shown to be indicators of comprehensive knowledge of HIV/AIDS. Policymakers and public health practitioners in India should come up with plans to close the information gaps about HIV/AIDS that exist among women and their demographic subgroups.