Key landscape exposure to multiple stressors (wildfire, insects and disease, urban and exurban development, and climate change) can pose risks to human health, biodiversity and ecosystem services. New maps reveal that much of the conterminous United States (CONUS) will be exposed to these stressors and unprecedented climate change by the middle of the century. The arrival of record setting temperatures will most likely be both rapid and widespread within the CONUS if greenhouse gas emissions continue to rise throughout the 21st century. By 2060, 91 percent of the CONUS could depart from the prevailing climate of the last century. Although much of the CONUS (37 percent) could be impacted by at least one of the landscape stressors examined, multiple coinciding stressors are likely to affect less than 9 percent of the CONUS. The two most prevalent coinciding stressors are (1) wildfire potential combined with insect disease risk, and (2) climate departure combined with urban and exurban development. Combined exposure to three or more stressors was rare, but are likely to affect several localized high-population areas.