•We documented the highest infective rate by Leishmania in anthropophilic sand flies so far reported in Mexico.•Based on the biting rate and the infective biting rate of Phlebotomine sandflies, the potential increase in entomological and epidemiological exposure to L. (L.) mexicana continues to be associated primarily with conserved forests.•Our study also detected that, albeit to a lesser extent, human exposure to Leishmania is occurring in environments with intermediate and high disturbance.•Change in land use did not influence the pattern of nocturnal exposition to anthropophilic Phlebotomine sand fly.•Although temperature and humidity vary between sites with different land uses, these variables are not related to the biting rate or the infective biting rate of Phlebotomine sand flies. Could tropical forest conversion shape sand fly (Diptera: Phlebotominae) biting rhythms and Leishmania infection rates? Using a Shannon trap, we estimated the bite rate and infection prevalence among anthropophilic sand flies at sites with different land use in southern Mexico. We estimated the expected monthly infection rate of the Leishmania parasite along the gradient and generated information on the biting rhythm of sand flies in a poorly characterized cutaneous leishmaniasis endemic region. We used generalized mixed linear and mixed additives models to evaluate differences in the biting rate, nocturnal activity, and inoculation rate of female sand flies, as well as their relationship with the loss of forest cover and environmental disparities recorded throughout the study area. Our results show that the loss of forest cover influences the biting rhythm of sand fly species and the potential number of infectious bites with Leishmania, but the greatest entomological and potential epidemiological risk continues to be associated with sylvatic areas (amplification events). Despite this, we detected that the effect of forest cover (%) on the entomological exposure seems to be also dependent on the sand fly species, and that, albeit to a lesser extent, Leishmania parasite is circulating in disturbed landscapes through generalist and competent sand fly vector species. We also found that land use change did not affect the nocturnal activity, however we detected that important vector species were active most of the time. Contrary to our expectation, temperature and humidity did not shape the biting rhythm of sand fly species. We discuss the limitations and epidemiological implications of our findings regarding the risk of contracting leishmaniasis in southern Mexico.