The World Health Organization (WHO) recognized Buruli ulcer (BU), a skin disease caused by Mycobacterium ulcerans (MU), as the third most prevalent mycobacterial disease in 1998, following tuberculosis and leprosy. In Ghana, there have been over 2000 reported cases in the past decade, with outbreaks in 90 administrative districts, including Amansie West. The mode of transmission remains unclear, but research suggests water bugs may be involved. This study aimed to assess this transmission method by identifying potential water bug habitats using geospatial techniques. Water bugs are found to inhabit freshwater ponds, marshes, slow-moving pools, streams, and mats of vegetation. This study used the Normalized Difference Water Index (NDWI) to locate water bodies and marshy areas, the Atmospherically Resistant Vegetation Index (ARVI) to identify vegetation zones, and Land Surface Temperature (LST) to determine suitable areas for water bugs based on temperature. A spatial multi-criteria evaluation (MCE) pinpointed critical areas for Mycobacterium ulcerans-hosting water bugs, which were mainly located in illegal mining areas due to stagnant wastewater. Notably, 36 communities, including prominent ones like Manso Nkwanta and Pakyi Number 1 and 2, were situated within these critical zones. This study generated a geospatial distribution map highlighting the potential areas for Mycobacterium ulcerans-hosting water bugs in the Amansie West district, crucial for Buruli ulcer transmission. The study recommended improved environmental sanitation in the affected areas to combat this water bug-related health issue.