Background. In spite of global decline in under-five mortality, the goal of achieving MDG 4 still remains largely unattained in low and middle income countries as the year 2015 closes-in. To accelerate the pace of mortality decline, proven interventions with high impact need to be implemented to help achieve the goal of drastically reducing childhood mortality. This paper explores the association between socio-economic and demographic factors and under-five mortality in an impoverished region in rural northern Ghana. Methods. We used survey data on 3975 women aged 15–49 who have ever given birth. First, chi-square test was used to test the association of social, economic and demographic characteristics of mothers with the experience of under-five death. Subsequently, we ran a logistic regression model to estimate the relative association of factors that influence childhood mortality after excluding variables that were not significant at the bivariate level. Results. Factors that significantly predict under-five mortality included mothers’ educational level, presence of co-wives, age and marital status. Mothers who have achieved primary or junior high school education were 45% less likely to experience under-five death than mothers with no formal education at all (OR = 0.55, p < 0.001). Monogamous women were 22% less likely to experience under-five deaths than mothers in polygamous marriages (OR = 0.78, p = 0.01). Similarly, mothers who were between the ages of 35 and 49 were about eleven times more likely to experience under-five deaths than those below the age of 20 years (OR = 11.44, p < 0.001). Also, women who were married had a 27% less likelihood (OR = 0.73, p = 0.01) of experiencing an under-five death than those who were single, divorced or widowed. Conclusion. Taken independently, maternal education, age, marital status and presence of co-wives are associated with childhood mortality. The relationship of these indicators with women’s autonomy, health seeking behavior, and other factors that affect child survival merit further investigation so that interventions could be designed to foster reductions in child mortality by considering the needs and welfare of women including the need for female education, autonomy and socioeconomic well-being.