During the last deglaciation (18–8 kyr BP), shelf flooding and warming presumably led to a large-scale decomposition of permafrost soils in the mid-to-high latitudes of the Northern Hemisphere. Microbial degradation of old organic matter released from the decomposing permafrost potentially contributed to the deglacial rise in atmospheric CO2 and also to the declining atmospheric radiocarbon contents (Δ14C). The significance of permafrost for the atmospheric carbon pool is not well understood as the timing of the carbon activation is poorly constrained by proxy data. Here, we trace the mobilization of organic matter from permafrost in the Pacific sector of Beringia over the last 22 kyr using mass-accumulation rates and radiocarbon signatures of terrigenous biomarkers in four sediment cores from the Bering Sea and the Northwest Pacific. We find that pronounced reworking and thus the vulnerability of old organic carbon to remineralization commenced during the early deglaciation (∼16.8 kyr BP) when meltwater runoff in the Yukon River intensified riverbank erosion of permafrost soils and fluvial discharge. Regional deglaciation in Alaska additionally mobilized significant fractions of fossil, petrogenic organic matter at this time. Permafrost decomposition across Beringia’s Pacific sector occurred in two major pulses that match the Bølling-Allerød and Preboreal warm spells and rapidly initiated within centuries. The carbon mobilization likely resulted from massive shelf flooding during meltwater pulses 1A (∼14.6 kyr BP) and 1B (∼11.5 kyr BP) followed by permafrost thaw in the hinterland. Our findings emphasize that coastal erosion was a major control to rapidly mobilize permafrost carbon along Beringia’s Pacific coast at ∼14.6 and ∼11.5 kyr BP implying that shelf flooding in Beringia may partly explain the centennial-scale rises in atmospheric CO2 at these times. Around 16.5 kyr BP, the mobilization of old terrigenous organic matter caused by meltwater-floods may have additionally contributed to increasing CO2 levels.