BACKGROUND: More than 90% of babies acquire HIV/AIDS through vertical transmission, primarily due to low maternal comprehensive knowledge about Mother-To-Child Transmission (MTCT) of HIV/AIDS and its prevention, which is a cornerstone for eliminating MTCT of HIV/AIDS. However, there are limitations in terms of population data and literature evidence based on recent Demographic and Health Surveys (DHS) reports in East Africa. Therefore, this study aims to assess the comprehensive knowledge and PMTCT of HIV/AIDS among women, as well as the associated factors in East Africa. METHODS: Our data was obtained from the most recent DHS conducted in East African countries between 2011 and 2022. For our research, we included DHS data from ten nations, resulting in a total weighted sample of 133,724 women for our investigation. A generalized linear model (GLM) with a log link and binomial family to directly estimate prevalence ratios (PR) and 95% confidence intervals (CI) for the association between the independent variables, and the outcome variable. Finally, we reported the adjusted prevalence ratios along with their corresponding 95% CIs. Factors with p-values ≤ 0.2 for univariate logistic regression and < 0.05 were considered statistically significant factors of HIV/AIDS knowledge and prevention in the final model. RESULTS: In this study, 59.41% (95% CI: 59.15-59.67) of respondents had a comprehensive knowledge about MTCT of HIV/AIDS and its prevention among reproductive-age women in East Africa. Being in the older age group, better education level, being from a rich household, employment status, having ANC follow up, institutional delivery, and modern contraception usage were associated with higher prevalence ratios of comprehensive knowledge about MTCT of HIV/AIDS and its prevention. However, being single in marital status, rural women, and traditional contraception utilization were associated with lower ratios of comprehensive knowledge about MTCT of HIV/AIDS and its prevention. CONCLUSION: Our findings indicate a significant deficiency in comprehensive knowledge and prevention of HIV/AIDS MTCT among women in East Africa. These results emphasize the need for significant improvements in maternal-related health services. It is crucial to effectively target high-risk populations during interventions, raise awareness about this critical public health issue, and address the catastrophic consequences associated with MTCT. By implementing these measures, we can make substantial progress in reducing the transmission of HIV/AIDS from mother to child and ensuring better health outcomes for both mothers and their children.