- Relatively little research has been conducted on the place of health literacy (HL) as an essential mechanism to achieve the Sustainable Development Goal for gender equality (SDG 5) or to enhance its role in SDG 3, good health and well-being, particularly in sub-Saharan Africa (SSA). The present analyses examined the role of socio-economic, health and behavioral factors associated with HL among men and women in the Ashanti Region of Ghana using a cross-sectional design and data collected from 779 rural and urban residents from June 2015 to October 2015. HL was higher among men. In multivariate logistic regression analyses, income and education were positively associated with HL for both men and women. Ethnicity showed a positive relationship with HL among men, while religious affiliation was associated with HL of overall population. Smoking was negatively associated with HL among men. Among women, self-reported health was positively associated with HL but having health insurance was inversely related. These gender differences may be due to dominant male gender roles and differing expectations and opportunities for socio-economic advancement for men and women. An inter-disciplinary approach is suggested for understanding and improving HL in both genders and especially in women, given their current low HL.