Introduction: Globally there were 37.7 million people living with Human Immunodeficiency Virus (HIV). HIV is a major global public health problem with disproportionally highest burden in sub-Saharan Africa accounting 70% of the global burden of infection.Objective: To assess factors associated with comprehensive knowledge on HIV among reproductive-age women in GambiaMethods: This study was based on a large community-based cross-sectional survey, conducted from 21 November 2019 to 30 March 2020 in Gambia. The survey employed a stratified two-stage cluster sampling technique to recruit study participants. Descriptive statistics and logistic regression models were used to summarize descriptive data and identify factors associated with HIV comprehensive knowledge respectively. A p-value of less than 0.05 and 95% confidence interval were used to determine statistical significance.Results: A total of 11,865 weighted sample of reproductive age women were included in the study with a mean age of 28.21(±9.33) which ranges from 15 to 49 years. Older age (AOR=1.21 (95%CI: 1.17,1.25)),being married (AOR=0.71 (95%CI: 0.61, 0.81)), using contraceptive (AOR=1.15 (95%CI: 1.01, 1.31)),secondary and higher education (AOR=2.17(95%CI:1.91, 2.45)),and(AOR=4.73 (95%CI: 3.86, 5.81)) respectively, middle and rich wealth quintile (AOR=1.29 (95%CI:1.11, 1.49)),and (AOR=1.61 (95%CI: 1.37, 1.87)), media exposure (AOR=1.76 (95%CI:1.39, 2.23)), ever tested for HIV (AOR=1.56 (95%CI: 1.41,1.73)), used internet (AOR=1.43 (95%CI:1.28,1.59)) and visited health facility within the last 12 months( AOR=1.26(95%CI:1.13,1.40)) were significantly associated with comprehensive HIV knowledge.Conclusion: socio-demographic factors, contraceptive use, media exposure, tested for HIV, internet use and visiting health facility was significantly and positively associated with comprehensive HIV knowledge except being married and residing in Basse region in which they associated negatively and significantly. Health managers, policy makers and intended stakeholders working on this area should consider those factors while designing health intervention programs to enhance comprehensive HIV knowledge among reproductive age women. Educational interventions about HIV/AIDS prevention mechanisms should be designed especially for married women and lower socio-economic status .Efforts has to be made to address those disparities at the national level.