As changes in the environment have brought wild and domestic animals into closer proximity, cross-species disease transmission has become a major concern in wildlife conservation. The worldwide impacts of tick-borne diseases require an understanding of pathogen transmission dynamics across different host species. Livestock are often kept near protected areas and frequently share habitat with wild animals. The influence of host community composition on tick-borne pathogen transmission remains poorly understood, making it difficult to determine whether sharing habitats with domestic livestock increases tick-borne disease in wildlife populations. We used network analysis to analyse 35,349 collections of 54 tick species in South Africa, treating hosts as nodes and shared tick species as links. Across all life stages, 93 mammalian species were connected by a total of 3105 links. Sheep, goats, and dogs were particularly important domestic species for network connectivity; and for wild animals, soft-skinned, smaller mammals such as the scrub hare. Although South African ticks exhibit some specialization on wild animals, network analysis showed that opportunistic feeding on domestic hosts can lead to shortened transmission pathways and facilitate pathogen spread between mammal species. Mammal species are highly interconnected through the tick species that they share, and domestic mammals significantly increase the risk of disease transmission. These findings support conservation measures that limit contact between domestic and wild mammals to reduce tick-borne disease transmission. Grazing in protected areas must be evaluated in light of disease risks to both domestic and wild animals, and potentially also to people.