Ghana’s current population is about 24.2 million, and given the current population growth rate of 2.4 %, Ghana’s population is expected to double in about 29 years. Although fertility rates in Ghana have declined from 6.4 to 4 children per woman between 1988 and 2008, this transition has not been homogenous across all regions of Ghana. Fertility rates remain higher in the northern regions of the country, compared to the southern regions. This paper examines explanations for the regional fertility variations—particularly the persistently high fertility rates observed in the northern regions—paying particular attention to the contribution of socioeconomic, cultural and religious factors, and fertility attitudes among women in explaining this phenomenon. In order to capture the most recent fertility variations in the country, the paper uses the most recent round (2008) of the Ghana Demographic and Health Survey, and employs a Poisson multivariate estimation technique. Results indicate that regional differences in fertility are largely explained by socioeconomic factors such as urbanization, child mortality, education and household wealth. Cultural and religious factors also explain some of the observed variation between the northern region and the southern regions. The inclusion of the duration of post-partum amenorrhea and other proximate determinants in the model specifications significantly explains residual differences in fertility outcomes, particularly among the three northern regions. Findings therefore indicate a need for more region-specific policy targeting in the effort to reduce high fertility rates and ease the growth in population.