Following the increased attention income differences/inequality has gained within the area of economic geography and among policy-planning; this study seeks to explore and analyze the factors affecting income differences in the regions of Ghana. From the use of regional (10 regions) panel data for 1960, 1970, 1984 and 2000; the results show a direct link between socio-demographic factors and regional income differences/inequality and also the impact of ethnic and religious composition on regional income differences. It was identified that ethnicity and religious compositions have different impacts on regional income differences. Christians have positive effect on regional income due to their fairly representation in almost all the regions likewise the Akans, but have negative effect on regional income. And also high population density in a region reduces the mean regional income, similarly high concentration of population aged 60years and over reduces the regional income. Evidence from the results empirically conclude that regions with high share of aged population, Akans, Muslims and high population density have low regional income compared with regions with high share of Christians.