America has an abundance of natural resources, such as plentiful surface and groundwater, forests, fertile land for agriculture, and minerals. These resources are vital to our health and well-being and to the Nation’s economic security. Natural toxins and environmental contaminants, the occurrence of undesired or excess amounts of chemicals or pathogens in environmental spaces, can threaten these resources or be a natural byproduct of resource use and extraction. A lack of understanding of the mechanisms by which these contaminants can cause adverse health effects represents an ongoing challenge as resource managers attempt to safeguard human and wildlife health. The USGS Environmental Health Program performs and delivers source-to-receptor One Health science to address the full range of questions related to contaminant and pathogen sources, environmental transport, exposure and transmission pathways, uptake, biological effects, and human health implications. Through these efforts, EH scientists are informing priorities, needs, and response strategies to address contaminant and pathogen exposures in wildlife and humans.