The Buruli ulcer infection occurs in well defined areas throughout the world, mostly tropical areas – in several areas in Australia, in Uganda, in several countries in West Africa, in Central and South America, in Southeast Asia and New Guinea. It is steadily rising as a serious disease, especially in West Africa and underdeveloped countries, where it is the third leading cause of mycobacterial infection in healthy people, after tuberculosis and leprosy. In East Africa, thousands of cases occur annually and in these areas the disease has displaced leprosy to become the second most important mycobacterial disease of man (after tuberculosis).

The disease is more likely to occur where there have been environmental changes such as the development of water storages, sand mining and irrigation.