The authors analyze the historical and spatial determinants of the implantation, persistence, and spread of cutaneous leishmaniasis in the municipality of Rio de Janeiro and the links between the disease and the organization of urban space and occupation processes on the periphery of the city beginning in the early 20th century through the 1980s. A pattern of outbreaks that was restricted and spatially discontinuous but sequenced was observed and seen to be linked to a dynamic process of urban real estate appreciation, comprising a large endemic area for cutaneous leishmaniasis. An analysis of the occupation and organization of urban space in the so-called Western Zone of Rio de Janeiro was conducted, considering new functions of spatial elements expressed through changing work relations, land use, and land value. Urbanization of the area produced the necessary conditions to intensify an endemic pattern of well-defined outbreaks where human mobility and the work process increased contact between susceptible individuals and vectors. Analysis showed spatial units with differentiated risk levels.