Chagas disease is a zoonosis caused by the parasite Trypanosoma cruzi and transmitted by insect vectors to several mammals, but little is known about its spatial epidemiology. We assessed the spatial distribution of T. cruzi infection in vectors and small mammals to test if mammal infection status is related to the proximity to vector colonies. During four consecutive years we captured and georeferenced the locations of mammal species and colonies of Mepraia spinolai, a restricted-movement vector. Infection status on mammals and vectors was evaluated by molecular techniques. To examine the effect of vector colonies on mammal infection status, we constructed an infection distance index using the distance between the location of each captured mammal to each vector colony and the average T. cruzi prevalence of each vector colony, weighted by the number of colonies assessed. We collected and evaluated T. cruzi infection in 944 mammals and 1976 M. spinolai. We found a significant effect of the infection distance index in explaining their infection status, when considering all mammal species together. By examining the most abundant species separately, we found this effect only for the diurnal and gregarious rodent Octodon degus. Spatially explicit models involving the prevalence and location of infected vectors and hosts had not been reported previously for a wild disease.