nternational Journal of One Health, 2017;3:66-76.Background: Anthrax is an infectious fatal zoonotic disease caused by Bacillus anthracis. Anthrax outbreak was confirmed in samples of wild animals following rumors of the outbreak in wild animals, livestock, and humans in Selela ward, Monduli district of Northern Tanzania. Therefore, a multi-sectorial team was deployed for outbreak response in the affected areas. Objectives: The aim of the response was to manage the outbreak in a One Health approach and specifically: (i) To determine the magnitude of anthrax outbreak in humans, livestock, and wild animals in Selela ward, (ii) to assess the outbreak local response capacity, (iii) to establish mechanisms for safe disposal of animal carcasses in the affected areas, and (iv) to mount effective control and preventive strategies using One Health approach in the affected areas. Materials and Methods: This was a cross-sectional field survey using: (i) Active searching of suspected human cases at health facilities and community level, (ii) physical counting and disposal of wild animal carcasses in the affected area, (iii) collection of specimens from suspected human cases and animal carcasses for laboratory analysis, and (iv) meetings with local animal and human health staff, political, and traditional leaders at local levels. We analyzed data by STATA software, and a map was created using Quantum GIS software. Results: A total of 21 humans were suspected, and most of them (62%) being from Selela ward. The outbreak caused deaths of 10 cattle, 26 goats, and three sheep, and 131 wild animal carcasses were discarded the majority of them being wildebeest (83%). Based on laboratory results, three blood smears tested positive for anthrax using Giemsa staining while two wildebeest samples tested positive and five human blood samples tested negative for anthrax using quantitative polymerase chain reaction techniques. Clinical forms of anthrax were also observed in humans and livestock which suggest that wild animals may contribute as reservoir of anthrax which can easily be transmitted to humans and livestock. Conclusion: The rapid outbreak response by multi-sectoral teams using a One Health approach managed to contain the outbreak. The teams were composed of animal and human health experts from national to village levels to control the outbreak. The study testifies the importance of multi-sectoral approach using One Health approach in outbreak preparedness and response.USAID through the Preparedness and Response (P &R) project (Grant No: AID – OAA - A – 14 – 00098, and Project No: Emerging Pandemic Threats – 2 phase [EPT -2]