American cutaneous leishmaniasis (CL) is a severely understudied and neglected“disease of poverty” widespread throughout Peru. Transmission dynamics of CL are complex, requiring sandfly vectors and mammalian reservoir hosts to maintain the pathogen in a local environment whereby incidental hosts (people) can become infected. We employed a One-Health approach to understand CL transmission in rapidly changing region of northern Peru. We describe the characteristics of 529 CL positive patients from four participating clinics. Using conditional logistic regression, we assessed risk factors of CL for residents of small urban areas through a matched case-control study with 63 patients who had visited one of the same clinics for CL (cases) or other medical reasons (controls). We later enrolled 343 households as part of a community based study occurring in 15 urban and rural areas of Soritor. We found 256 positive humans (n= 914) as tested via the Montenegro Skin Test; we found 11 positive dogs (n = 236) via an immunofluorescence antibody test. Our results suggest that most- if not all- of CL transmission is occurring in rural areas and that urban women and urban children engage in many high risk activities typically attributed to men. We find evidence that prevalence of past infection is highest among rural residents and men. We believe dogs are unlikely Leishmania reservoirs in either rural or urban settings. It remains unknown if the high number of MST positive children in rural areas is a result of peridomestic or intradomestic transmission.