Nigeria and Ghana are two Sub-Saharan African countries that are notoriously and incurably noted to be bedeviled by the prevalence of open defecation. Written thousands of years before the emergence of modern medicine, Deuteronomy 23:13 is one of the Old Testament Pentateuchal sanitary laws of God that provides an excellent model for dealing with the menace of open defecation. The text has hygienic undertones as it promotes proper disposal of human waste. In this article, the author harnesses various scholastic interpretations of the text to tackle open defecation challenges in Nigeria and Ghana. The author defines open defecation as the practice of emptying the bowels outside a designated toilet and argues that it hinders public health, pollutes water, and affects sanitation negatively. The article, through the biblical model, advocates for proper hygienic and environmental practices to help deal with the current sanitation threat. The article reviews literature from scholarly publications relevant to open defecation, with a focus on open defecation prevalence, factors influencing open defecation, and impacts in Nigeria and Ghana.