Exposure to zoonotic diseases can trade-off against livelihood-critical activities, particularly for tropical forest-dependent communities. Inter-disciplinary ecosystem approaches are critical to understanding this zoonotic spillover since the ecological and socio-political processes that make people vulnerable are jointly studied across degraded ecosystems. Moreover, One Health co-production of research and tools with cross-sectoral stakeholders can bridge gaps in knowledge and disease management between sectors. The MonkeyFeverRisk project applied these approaches to a case study of human viral tick-borne disease, Kyasanur Forest Disease (KFD), affecting forest-dependent communities in the Western Ghats, south India, to inform management. Multiple tick species and vertebrate hosts are involved in Kyasanur Forest Disease Virus transmission, including wild rodents and shrews, monkeys and birds, while humans are “dead-end” hosts contracting the disease when bitten by infected ticks. By sampling across habitats within fragmented forests, we found that the risk of human exposure to infected ticks extends outside forests to forest edges, plantations, houses and gardens. The highest risk of human spillover was found in diverse agro-forestry landscapes, created when the moist evergreen forest is replaced with plantations and rice cultivation. Risks and impacts of KFD were highest for socially vulnerable, marginalised groups (e.g. lower caste, landless, elderly-headed households), exposed to ticks through occupations in forests, plantations and cropland. Aside from mortality, disease impacts include long-term, debilitating health issues, loss of income and reduced forest access. Key barriers to effective KFD prevention within these communities included limited information about KFD and its transmission, low efficacy of and mistrust in currently available vaccines and tick repellents, and livelihood concerns. Co-production delivered web-based tools to guide management, identifying high-risk areas, and education materials for local communities, health workers and managers detailing risks from ticks and tick-bite prevention measures.