In East Africa, a region with many endemic and emerging zoonoses, and in countries such as Ethiopia in particular, One Health (OH) approaches are increasingly seen as effective ways, to mitigate the risk of zoonoses at the interface between human, animal and the environment. The OH approach promotes interdisciplinary cooperation and collaboration between researchers and practitioners from the disciplines of human, animal and environmental health. Moreover, it advocates for the establishment of a public health sector model which recognises the imperative to holistically address diseases that occur in the human, animal and environmental health arena.Key informant interviews were conducted with human and animal health practitioners and academic researchers in Ethiopia to collect data on the implementation of the OH approach to manage zoonotic diseases at the human and animal health interface. Participants' observations were undertaken within animal and human health clinics and government laboratories to gather additional data. Environmental health was not considered in this study as it is not yet fully integrated into the OH approach in Ethiopia.The results reveal a lack of interdisciplinary cooperation, collaboration, and coordination between animal and human health practitioners in operationalising the OH framework in Ethiopia. Professionals in academic and non-academic institutions and organisations are interested in implementing the OH approach, however, an organisational “silo” culture constrains collaboration between institutions dealing with animal and human health. Understaffing and underfunding of institutions were also cited as major challenges to the implementation of a OH approach. Lack of interdisciplinary training for animal and human health practitioners hinders collaboration in the management of zoonoses.Policymakers need to go beyond the rhetoric to a genuine focus on reform of health management and implement policies that bridge human, animal and environmental health. There is a need for multidisciplinary and transdisciplinary training in human, animal and environmental health and collaborative research for the management of zoonoses.