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Summary: The rapid global spread and human health impacts of SARS-CoV-2, the virus that causes COVID-19, show humanity's vulnerability to zoonotic disease pandemics. Although anthropogenic land use change is known to be the major driver of zoonotic pathogen spillover from wildlife to human populations, the scientific underpinnings of land use-induced zoonotic spillover have rarely been investigated from the landscape perspective. We call for interdisciplinary collaborations to advance knowledge on land use implications for zoonotic disease emergence with a view toward informing the decisions needed to protect human health. In particular, we urge a mechanistic focus on the zoonotic pathogen infect–shed–spill–spread cascade to enable protection of landscape immunity—the ecological conditions that reduce the risk of pathogen spillover from reservoir hosts—as a conservation and biosecurity priority. Results are urgently needed to formulate an integrated, holistic set of science-based policy and management measures that effectively and cost-efficiently minimise zoonotic disease risk. We consider opportunities to better institute the necessary scientific collaboration, address primary technical challenges, and advance policy and management issues that warrant particular attention to effectively address health security from local to global scales.