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Yersinia pestis, the causative agent of plague, has been detected in fleas and mammals throughout the western United States. This highly virulent infection is rare in humans, surveillance of the disease is expensive, and it often was assumed that risk of exposure to Y. pestis is high in most of the western United States. For these reasons, some local health departments in these plague-affected regions have hesitated to undertake surveillance and other prevention activities. To aid in targeting limited public health resources, we created a fine-resolution human plague risk map for New Mexico, the state reporting more than half the human cases in the United States. Our GIS-based model included three landscape features—a nonlinear relationship with elevation, distance to water, and distance to the ecotone between Rocky Mountain/Great Basin open and closed coniferous woodlands—and yielded an overall accuracy of ≈ 80%. The model classified 17.25% of the state as posing significant risk of exposure to humans on privately or tribally owned land, which suggests that resource requirements for regular surveillance and control of plague could be effectively focused on < 20% of the state.