Open defecation continuously remains a major global sanitation challenge, contributing to an estimated 1.6 million deaths per year. Ghana ranks second in Africa for open defecation and had the fourth-lowest sanitation coverage in 2010. Evidence indicates that about 32% of the rural Ghanaian population still practice open defecation due to lack of access to basic sanitation facilities, drifting the country from achieving universal access to sanitation by 2030. Women, particularly those in rural areas, are disproportionately affected by open defecation, facing heightened health risks, harassment, and a loss of dignity. Even though previous studies on open defecation in Ghana exist, they lack national representation and neglect women in rural residents who are disproportionally affected by the repercussions of open defecation. Examining that rural women will contribute to heightening their own vulnerability to health risks by practising open defecation is essential to bridging the literature gap on open defecation practices among rural women. The study investigated determinants of open defecation among rural women in Ghana using data from the female files of the 2003, 2008 and 2014 Demographic and Health Surveys (DHS). A total of 4,284 rural women with complete information on variables of interest were included in the study. The outcome variable was ‘open defecation’, whilst 14 key explanatory variables (e.g., age, education, wealth status, among others) were used. Two logistic regression models were built, and the outputs were reported in odds ratio. Descriptively, 42 in every 100 women aged 15 to 49 practiced open defecation (n = 1811, 95% CI = 49-52). Open defecation (OD) significantly correlated with educational attainment, wealth status, religion, access to mass media, partner’s education, and zone of residence. The likelihood of practicing open defecation reduced among those with formal education [aOR = 0.69, CI = 0.56-0.85], those whose partners had formal education [aOR = 0.64, CI = 0.52-0.80], women in the rich wealth quintile [aOR = 0.12, CI = 0.07-0.20], the traditionalist [aOR = 0.33, CI = 0.19-0.57], and those who had access to mass media [aOR = 0.70, CI = 0.57-0.85]. Residents in the Savannah zone had higher odds of openly defecating [aOR = 21.06, CI = 15.97-27.77]. The prevalence of open defecation is disproportionately pro-poor, which indicates that impoverished rural women are more likely to perform it. Public health initiatives should aim to close the rich-poor divide in OD practice among rural women.