Knowledge about the deglaciation history of the Greenland Ice Sheet (GrIS) is important to put the recent observations of ice loss into a longer-term perspective. In southern Greenland, the deglaciation history is generally well constrained. In this study, we use 43 new ¹⁰Be surface exposure ages combined with existing minimum-limiting ¹⁴C ages to constrain the deglaciation history of eastern North Greenland, including the three major fjord systems – Independence Fjord, Hagen Fjord and Danmark Fjord. The ¹⁰Be ages are generally scattered and many of the samples are significantly older than expected, with pre-LGM ages being a result of inheritance from previous exposures. By using a Bayesian statistical approach to combine the new ¹⁰Be ages and existing ¹⁴C ages, we are able to constrain the deglaciation history. We find that the outer coast and deep fjords were rapidly deglaciated between ̃11 and 10 ka. Subsequently, the deglaciation progressed far inland up the fjords, probably as a result of increased summer surface temperatures and subsurface ocean temperatures during the Holocene Thermal Maximum. The rapid retreat of the Middle Holocene slowed when the ice sheet became land-based in the central and southern part of the study area where the ice margin first reached its present extent by ̃6.7 ka. As the onset of Neoglacial ice advance had already commenced at ̃5 ka this limits the period when the ice margin could retreat farther inland and it probably remained within max. 30–40 km of its present extent. The contrasting behaviour between the fjords and inter-fjord areas shows a clear topographic effect on the stability of the GrIS. These results inform how the GrIS may respond to a warmer climate in various topographic settings and may provide useful constraints for future ice-sheet models.