Chagas disease is a zoonotic infectious disease, produced by the parasite Trypanosoma cruzi. Infection results principally from contact with parasite-contaminated bug feces, deposited during a triatomine vector’s blood meal. The vectors are ubiquitous in conserved and human-transformed landscapes, since they inhabit sylvatic mammal nests, but persist and disperse among human communities. Exposure to infected vectors occurs both in conserved habitats and along human-transformation gradients. Several studies have focused on biological determinants, but only a handful of studies analyze sociocultural determinants of transmission. We explore cultural and social patterns within landscapes that affect human exposure in Mayan populations of Yucatan state. Primary factors contributing to vector exposure are: the lack of knowledge regarding the consequences of insect blood feeding habits, houses susceptible to bug infestation, farming and land-use practices, hunting, and rural migration. Gender affects the differential contribution of all of these factors. Exposure is aggravated by deficient infection diagnosis and treatment options, which raise risk for all transmission modes (vector-borne, congenital, blood transfusion and organ transplant, or oral).