Buruli Ulcer is a devastating skin disease caused by the pathogen Mycobacterium ulcerans. Emergence and distribution of Buruli ulcer cases is clearly linked to aquatic ecosystems, but the specific route of transmission of M. ulcerans to humans remains unclear. Relying on the most detailed field data in space and time on M. ulcerans and Buruli ulcer available today, we assess the relative contribution of two potential transmission routes –environmental and water bug transmission– to the dynamics of Buruli ulcer in two endemic regions of Cameroon. The temporal dynamics of Buruli ulcer incidence are explained by estimating rates of different routes of transmission in mathematical models. Independently, we also estimate statistical models of the different transmission pathways on the spatial distribution of Buruli ulcer. The results of these two independent approaches are corroborative and suggest that environmental transmission pathways explain the temporal and spatial patterns of Buruli ulcer in our endemic areas better than the water bug transmission.