Lutzomyia longipalpis is the natural vector of Leishmania (Leishmania) infantum, but it is also permissive for several Leishmania species that are related to cutaneous leishmaniasis (CL). Maranhao State (Northeast of Brazil) is endemic for CL and has the highest number of cases of diffuse cutaneous leishmaniasis (DCL) in the country. It is a rare disease associated with a defective immune response mainly caused by L. (L.) amazonensis. Additionally, the number of immunosuppressed patients infected with the etiologic agents of CL has increased, including regions in which the main vectors of CL are rare. Therefore, we investigated whether Lu. longipalpis is able to transmit L. (L.) amazonensis to uninfected and immunosuppressed mice, resulting in CL. For that, 291 sand flies took an initial blood meal in mice infected with L. (L.) amazonensis. Of these, 17 underwent a second feeding on uninfected and immunosuppressed mice (of which 58.8% were also positive for Leishmania according to data on the dissection of the intestine). After 27 days of infection, these mice exhibited leishmaniotic lesions. The occurrence of parasites on the animal's skin was confirmed by limiting dilution and immunohistopathological analyses. Parasite DNA was also detected in paw lesions and inguinal lymph nodes. DNA sequencing confirmed the Leishmania species in insects and mice. The results confirmed the ability of Lu. longipalpis to become infected and experimentally transmit L. (L.) amazonensis to immunosuppressed rodents, resulting in leishmaniotic lesions. Our data open perspectives for the potential role of Lu. longipalpis in the epidemiology of urban cutaneous leishmaniasis, especially in immunosuppressed patients.