Recent dramatic and deadly increases in global wildfire activity have increased attention on the causes ofwildfires, their consequences, and how risk from wildfire might be mitigated. Here we bring together dataon the changing risk and societal burden of wildfire in the United States. We estimate that nearly 50 millionhomes are currently in the wildland–urban interface in the United States, a number increasing by 1 millionhouses every 3 y. To illustrate how changes in wildfire activity might affect air pollution and related healthoutcomes, and how these linkages might guide future science and policy, we develop a statistical modelthat relates satellite-based fire and smoke data to information from pollution monitoring stations. Usingthe model, we estimate that wildfires have accounted for up to 25% ofPM2.5(particulate matter withdiameter<2.5μm) in recent years across the United States, and up to half in some Western regions, withspatial patterns in ambient smoke exposure that do not follow traditional socioeconomic pollution expo-sure gradients. We combine the model with stylized scenarios to show that fuel management interventionscould have large health benefits and that future health impacts from climate-change–induced wildfiresmoke could approach projected overall increases in temperature-related mortality from climate change—but that both estimates remain uncertain. We use model results to highlight important areas for future re-search and to draw lessons for policy.