Rabies is a fatal neglected tropical zoonosis, and its significance for domestic herbivores in the rural cycle is probably associated with rainforest deforestation, livestock, and agricultural expansion. This epidemiological survey aimed to study the occurrence of rabies in bovines and equines in the state of Rondônia, located in the Brazilian's Legal Amazon, between the years 2002 and 2021, correlating these findings with the prophylactic strategies adopted by the local sanitary agency for rabies control. During this period, 201 cases were observed in bovines and 23 in equines. A downward trend in rabies incidence was observed for both domestic herbivores. Rabies did not show a higher occurrence in any specific time of the year, and epidemic periods varied during some years for bovines and equines. Using the Generalized estimating equations (GEE) method, a multiple model approach was obtained with the explanatory variables significantly associated with the decrease in rabies incidence in cattle and horses during the study period: the ratio of treated bats and ratio of vaccine doses sold. Furthermore, the ratio of printed educative material was positively associated with rabies incidence. Despite a decreasing trend in rabies occurrences in this Amazon rainforest area, likely due to the actions taken by the animal sanitary agency, rabies remains endemic and requires monitoring, as well as prophylactic strategies to control this disease.