Abstract Background Rabies has a worldwide distribution in continental regions of Africa, Asia and the Latin America. Globally, the case fatality rate is 100% once a clinical sign is developed. Poor public awareness towards rabies is one of the major obstacles in any prevention and control scheme of the diseases. The study aimed to assess knowledge, attitude and practice (KAP) about rabies and associated factors among household heads in Mekelle city, Northern Ethiopia, 2016. Methods A community based cross-sectional study was conducted from October to November 2016 with a total of 633 study participants. Data were collected using a pretested structured questionnaire and entered to EPI-Info 3.5.4 and coded, cleaned and analyzed using SPSS version 20 software. Bi variable and multivariable analysis was done to identify factors associated with knowledge, attitude and practice about rabies. Variables having p