Background: Anthrax is prioritized as the second diseases in Ethiopia based on its negative impacts at the household level by causing disease or production losses in livestock and sever disease in human. This study aimed at assessing the knowledge, attitude and practices (KAPs) of anthrax in the communities of Eastern Tigray, Northern Ethiopia. Methods: A cross-sectional survey was concurrently conducted with focus group discussions (FGD) and key informant interviews (KII) from May 2019 to April 2020. A total of 862 respondents have participated in the questionnaire survey. Of which, 800 were local community members. While 62 were professionals working at animal and human health service institutions. Likewise, qualitative data were collected using six FGDs and 11 KIIs. Results: sixty two percent (496/800) of the respondents said that they knew the disease anthrax while 38% (304/800) of them did not it. Only 9.3% (74/800) of the respondents reported germ as the causative agent of anthrax. About 56.5% (35/62) of the professional respondents said that the causative agent of the disease was bacteria while 33.9% (21/62) of them did not know it. More than sixty percent (64.1%, 513/800) of the respondents did not know whether the disease was zoonotic or not. Among the listed clinical signs, 26.3% (210/800) and 36.8% (294/800) of the respondents knew at least one signs in animal and human, respectively while 21.3% (170/800) and 20.1% (161/800) knew one or more transmission routes in animal and human respectively. Moreover, 43.4% (347/800) and 45.6% (365/800) of the respondents mentioned one or more control/prevention method in animal and human, respectively. Regarding qualitative results, some of the participants knew the disease (in animals) in their own local names, Lalish and Tafia (splenomegaly), and Gulbus (abdominal cramp and shivering). Some had perceived the disease only as human disease while others recognized after they were told its clinical signs in animals and humans. Conclusion: The KAP of the participants towards anthrax was low. There was no similar understanding of the disease among the participants. The study also revealed that the participants did not get consistent, adequate and continuous health messages regarding the disease.