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Anthrax, a neglected zoonotic disease that is transmitted by a spore-forming, rod-shaped bacterium, Bacillus anthracis, has reached endemic proportions in the Western Province of Zambia. Transmission of anthrax from the environment as well as between cattle has been observed to be partly because of entrenched beliefs, perceptions and traditional practices among cattle farmers in the known outbreak areas. This study was aimed at exploring lay perceptions, beliefs and practices that influence anthrax transmission in cattle of the Western Province. A mixed-methods study was conducted from August to December 2015. Quantitative data were collected using a cross-sectional survey. Qualitative data were generated by interviewing professional staff and community members. Five focus group discussions and five key informant interviews were conducted. Thematic analysis of interview data was performed using NVivo software. The findings suggested that cattle anthrax was biologically as well as culturally maintained. Cattle farmers were reluctant to have their livestock vaccinated against anthrax because of perceived low efficacy of the vaccine. Also, the cattle farmers did not trust professional staff and their technical interventions. Popular cultural practices that involved exchange of animals between herds contributed to uncontrolled cattle movements between herds and subsequent transmission of anthrax. These findings imply the need for professional staff to be culturally competent in handling socio-cultural issues that are known to be barriers for disease control in animals. There is a need to develop a policy framework that will foster integrated control of anthrax across disciplines.