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Environmental impact assessments for new Arctic infrastructure do not adequately consider the likely long-term cumulative effects of climate change and infrastructure to landforms and vegetation in areas with ice-rich permafrost, due in part to lack of long-term environmental studies that monitor changes after the infrastructure is built. This case study examines long-term (1949–2020) climate- and road-related changes in a network of ice-wedge polygons, Prudhoe Bay Oilfield, Alaska. We studied four trajectories of change along a heavily traveled road and a relatively remote site. During 20 years prior to the oilfield development, the climate and landscapes changed very little. During 50 years after development, climate-related changes included increased numbers of thermokarst ponds, changes to ice-wedge-polygon morphology, snow distribution, thaw depths, dominant vegetation types, and shrub abundance. Road dust strongly affected plant-community structure and composition, particularly small forbs, mosses, and lichens. Flooding increased permafrost degradation, polygon center-trough elevation contrasts, and vegetation productivity. It was not possible to isolate infrastructure impacts from climate impacts, but the combined datasets provide unique insights into the rate and extent of ecological disturbances associated with infrastructure-affected landscapes under decades of climate warming. We conclude with recommendations for future cumulative impact assessments in areas with ice-rich permafrost.