Rapid fluctuations in the velocity of Greenland Ice Sheet (GIS) outlet glaciers over the past decade have made it difficult to extrapolate ice-sheet change into the future. This significant short-term variability highlights the need for geologic records of preinstrumental GIS margin fluctuations in order to better predict future GIS response to climate change. Using 10Be surface exposure ages and radiocarbon-dated lake sediments, we constructed a detailed chronology of ice-margin fluctuations over the past 10 k.y. for Jakobshavn Isbræ, Greenland's largest outlet glacier. In addition, we present new estimates of corresponding local temperature changes using a continuous record of insect (Chironomidae) remains preserved in lake sediments. We find that following an early Holocene advance just prior to 8 ka, Jakobshavn Isbræ retreated rapidly at a rate of ∼100 m yr−1, likely in response to increasing regional and local temperatures. Ice remained behind its present margin for ∼7 k.y. during a warm period in the middle Holocene with sustained temperatures ∼2 °C warmer than today, then the land-based margin advanced at least 2–4 km between A.D. 1500–1640 and A.D. 1850. The ice margin near Jakobshavn thus underwent large and rapid adjustments in response to relatively modest centennial-scale Holocene temperature changes, which may foreshadow GIS response to future warming.