Wilderness areas are not immune to changes in land use, land cover, and/or climate. Future changes will intensify the balancing act of maintaining ecological conditions and untrammeled character within wilderness areas. We assessed the quantitative and spatial changes in land use, land cover, and climate predicted to occur in and around wilderness areas by (1) quantifying projected changes in land use and land cover around wilderness areas; (2) evaluating if public lands surrounding wilderness areas can buffer future land-use change; (3) quantifying future climate conditions in and around wilderness areas; and (4) identifying wilderness areas expected to experience the most change in land use, land cover, and climate. We used projections of land use (four variables), land cover (five variables), and climate (nine variables) to assess changes for 707 wilderness areas in the contiguous United States by mid-21st century under two scenarios (medium-low and high). We ranked all wilderness areas relative to each other by summing and ranking decile values for each land use, land cover, and climate variable and calculating a multivariate metric of future change. All wilderness areas were projected to experience some level of change by mid-century. The greatest land-use changes were associated with increases in agriculture, clear cutting, and developed land, while the greatest land cover changes were observed for grassland, forest, and shrubland. In 51.6% and 73.8% of wilderness areas, core area of natural vegetation surrounding wilderness was projected to decrease for the medium-low and high scenarios, respectfully. Presence of public land did not mitigate the influence of land-use change around wilderness areas. Geographically, projected changes occurred throughout the contiguous U.S., with areas in the northeast and upper Midwest projected to have the greatest land-use and climate change and the southwestern U.S. projected to undergo the greatest land cover and climate change. Our results provide insights into potential future threats to wilderness areas and the challenges associated with wilderness stewardship and climate adaptation. Despite the high degree of protection and remoteness of wilderness areas, effective management and preservation of these lands must consider future changes in land use, land cover, and climate. © 2021 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.