This paper hypothesizes that arsenic in drinking water indirectly contributes to Buruli ulcer (BU), a skin disease caused by Mycobacterium ulcerans (MU) infection. Samples of groundwater and surface water used as drinking water by the population in Ghana’s Amansie West district (part of which has a high prevalence of BU), were collected near rural settlements and analysed for arsenic. Arsenic concentration levels per settlement were compared with BU prevalence. A positive exposure-response relationship was obtained between arsenic in surface water and BU (r2 = 0.82). However, there is no significant exposure-response relation between groundwater and BU.