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 aim of this study was 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 pre-tested structured questionnaire in Enderta district, Tigray regional state, Ethiopia. Data was entered to EPI-Info 3.5.4 and coded, cleaned and analyzed using SPSS version 20 software. Bivariable and multivariable analysis was done to identify factors associated with knowledge, attitude and practice about rabies. Variables having p< 0.05 was considered as statistically significant at 95%CI. Results: Of 633 study participants, 357 (56.4%) were females and 239 (37.8%) were 18-35 years old. Among the study participants, 56.1% (95%CI=52.2, 59.9), 56.2% (95%CI=52.4, 60.1) and 61.3% (95%CI=57.5, 65.1) had good level of knowledge, attitude and practice on the prevention and control of rabies respectively. Being female (AOR=1.50, 95%CI=1.05, 2.13), dog owner (AOR=1.68, 95%CI=1.17, 2.41) and participants who had training on rabies (AOR=2.22, 95%CI=1.53, 3.21) were found to have good knowledge. Married participants (AOR=2.19, 95%CI=1.16, 4.16), participants who owned dog (AOR=2.64, 95%CI=1.80, 3.86) and those encountered dog bite (AOR=2.24, 95%CI=1.23, 4.10) were found to have positive attitude towards rabies. Similarly dog ownership (AOR=11.85, 95%CI=7.16, 19.6) was found to be associated with good practice. Conclusion: This study showed that more than half of the respondents had good knowledge, attitude and practice about the prevention and control of rabies. Key words: Attitude, Community, Knowledge, Practice, Rabies