BackgroundRabies is a zoonotic disease that has been prevalent in humans and animals for centuries in Ethiopia and it is often dealt with using traditional practices. There is lack of accurate quantitative information on rabies both in humans and animals in Ethiopia and little is known about the awareness of the people about the disease. In this study, we estimated the incidence of rabies in humans and domestic animals, and assessed the people's awareness about the disease in North Gondar zone, Ethiopia.Methodology/Principal FindingsThe incidence of rabies in humans and domestic animals was prospectively followed up for one year period based on clinical observation. A questionnaire was also administered to 120 randomly selected dog owners and 5 traditional healers to assess the knowledge and practices about the disease. We found an annual estimated rabies incidence of 2.33 cases per 100,000 in humans, 412.83 cases per 100,000 in dogs, 19.89 cases per 100,000 in cattle, 67.68 cases per 100,000 in equines, and 14.45 cases per 100,000 in goats. Dog bite was the source of infection for all fatal rabies cases. Ninety eight percent of the questionnaire respondents were familiar with rabies and mentioned dog bite as a means of transmission. But discordant with current scientific knowledge, 84% and 32% of the respondents respectively mentioned any type of contact (irrespective of skin condition) with saliva, and inhalation as a means of transmission of rabies. Eighty four percent of the respondents relied on traditional healers for management of rabies.ConclusionsThe study shows high canine rabies burden, and lack of sufficient awareness about the disease and high reliance on traditional treatment that interfere with timely post exposure management. Vaccination of dogs, proper post exposure management, and increasing the awareness of the community are suggested to reduce the disease burden.