Tropical environments are known for their prevalence of a number of geochemical diseases. These are related to the very
nature of their geological settings. Little research has, however, been conducted in geosciences in Ghana to investigate the link between geological settings and Buruli Ulcer (BU) disease. This research therefore examined the effect of geological settings on the spread of BU disease caused by Mycobacterium Ulcerans (MU) in the Upper Denkyira West District (UDWD), Amansie West District (AWD) with Tarkwa Nsuaem Municipality (TNM) as a case control study area. Geological maps of the study areas were extracted from the geological map of Ghana. Epidemiological data of BU disease collected from the National Buruli Ulcer Control Programme, district hospitals and from fieldwork were overlaid on geological maps of the study areas. Spatial analysis was then performed to identify the relationship between geological settings and BU disease spread in the study areas. Twenty-seven (27) communities were found to have cases of BU in the three study areas. Results also show that districts underlain by Birimian meta-sedimentary rock units which mainly contain minerals like of pyrites and arsenopyrites are more susceptible to BU disease than districts underlain by Tarkwaian siliciclastics and Birimian meta-volcanic rocks. This research thus offers an opportunity to link geological settings and BU disease as well as contributes to public health and environmental management in the study areas.