Carbon cycle models suggest that past warming events in the Arctic may have caused large-scale permafrost thaw and carbon remobilization, thus affecting atmospheric CO2 levels. However, observational records are sparse, preventing spatially extensive and time-continuous reconstructions of permafrost carbon release during the late Pleistocene and early Holocene. Using carbon isotopes and biomarkers, we demonstrate that the three most recent warming events recorded in Greenland ice cores—(i) Dansgaard-Oeschger event 3 (~28 ka B.P.), (ii) Bølling-Allerød (14.7 to 12.9 ka B.P.), and (iii) early Holocene (~11.7 ka B.P.)—caused massive remobilization and carbon degradation from permafrost across northeast Siberia. This amplified permafrost carbon release by one order of magnitude, particularly during the last deglaciation when global sea-level rise caused rapid flooding of the land area thereafter constituting the vast East Siberian Arctic Shelf. Demonstration of past warming-induced release of permafrost carbon provides a benchmark for the sensitivity of these large carbon pools to changing climate.