High-latitude lakes are important for terrestrial carbon dynamics and waterfowl habitat driving a need to better understand controls on lake area changes. To identify the existence and cause of recent lake area changes in the Yukon Flats, a region of discontinuous permafrost in north central Alaska, we evaluate remotely sensed imagery with lake water isotope compositions and hydroclimatic parameters. Isotope compositions indicate that mixtures of precipitation, river water, and groundwater source ~95% of the studied lakes. The remaining minority are more dominantly sourced by snowmelt and/or permafrost thaw. Isotope-based water balance estimates indicate 58% of lakes lose more than half of inflow by evaporation. For 26% of the lakes studied, evaporative losses exceeded supply. Surface area trend analysis indicates that most lakes were near their maximum extent in the early 1980s during a relatively cool and wet period. Subsequent reductions can be explained by moisture deficits and greater evaporation.