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Fires in the wildland-urban interface (WUI) are a global issue with growing importance. However, the impact of WUI fires on air quality and health is less understood compared to that of fires in wildland. We analyze WUI fire impacts on air quality and health at the global scale using a multi-scale atmospheric chemistry model—the Multi-Scale Infrastructure for Chemistry and Aerosols model (MUSICA). WUI fires have notable impacts on key air pollutants [e.g., carbon monoxide (CO), nitrogen dioxide (NO₂), fine particulate matter (PM_2.5), and ozone (O₃)]. The health impact of WUI fire emission is disproportionately large compared to wildland fires primarily because WUI fires are closer to human settlement. Globally, the fraction of WUI fire–caused annual premature deaths (APDs) to all fire–caused APDs is about three times of the fraction of WUI fire emissions to all fire emissions. The developed model framework can be applied to address critical needs in understanding and mitigating WUI fires and their impacts.