Underweight prevalence among preschool children in Africa has been studied, but the effects of culture and geography remain unclear. This study used the 2008 Ghana Demographic and Health Survey data for 2244 children aged 0‐59 months and generalized linear mixed models to analyze these data. The results showed that culture and geography remained significantly associated with preschool underweight prevalence after controlling for demographic and socioeconomic characteristics of children, mothers, and households. Additionally, the gender of a child, size at birth, fever status, mother's BMI, insurance coverage and number of children <5 years in the household were significantly associated with underweight prevalence in Ghana. The study concluded that in addition to specific characteristics of children, mothers, and households, culturally motivated childhood dietary restrictions among the Ga/Dangme and Ewe could be reduced through appropriately targeted nutritional messages. Additionally, decreasing North‐South disparities in socioeconomic development, and improving nutritional outcomes among disadvantaged households in southern Ghana should be the focus of policies and strategies directed at reducing preschool underweight prevalence in Ghana.