Human activities are altering many factors that determine the fundamental properties of ecological and social systems. Is sustainability a realistic goal in a world in which many key process controls are directionally changing? To address this issue, we integrate several disparate sources of theory to address sustainability in directionally changing social–ecological systems, apply this framework to climate-warming impacts in Interior Alaska, and describe a suite of policy strategies that emerge from these analyses. Climate warming in Interior Alaska has profoundly affected factors that influence landscape processes (climate regulation and disturbance spread) and natural hazards, but has only indirectly influenced ecosystem goods such as food, water, and wood that receive most management attention. Warming has reduced cultural services provided by ecosystems, leading to some of the few institutional responses that directly address the causes of climate warming, e.g., indigenous initiatives to the Arctic Council. Four broad policy strategies emerge: (i) enhancing human adaptability through learning and innovation in the context of changes occurring at multiple scales; (ii) increasing resilience by strengthening negative (stabilizing) feedbacks that buffer the system from change and increasing options for adaptation through biological, cultural, and economic diversity; (iii) reducing vulnerability by strengthening institutions that link the high-latitude impacts of climate warming to their low-latitude causes; and (iv) facilitating transformation to new, potentially more beneficial states by taking advantage of opportunities created by crisis. Each strategy provides societal benefits, and we suggest that all of them be pursued simultaneously.