Knowledge about the future response of the Greenland Ice Sheet to global climate change, including ice sheet contributions to sea level rise, is important for understanding the impact of climate change on society. Such studies rely in ice sheet model predictions and improved chronological constraints of past ice sheet extents and paleoclimatic trends. Many regions in Greenland are well studied, but northwest Greenland and especially Melville Bay, being one of the most important regions in terms of dynamical ice mass loss, lack a firm chronology of Holocene ice marginal fluctuations. In this study, we present the first comprehensive chronology for Melville Bay spanning 73.1–75.7°N based on 36 new ¹⁰Be exposure ages of boulders and 39 new radiocarbon ages of marine molluscs in Little Ice Age moraines. From weighted mean ¹⁰Be exposure ages, excluding 6 outliers, we find that the outer coast in Melville Bay was deglaciated ∼11.6 ± 0.3 ka (n = 15) and the ice margin reached its present-day position 40 km farther inland ∼11.5 ± 0.3 ka (n = 15). Our results suggest an interval of rapid ice-marginal retreat (i.e. collapse) of the northwest GrIS in Melville Bay, most likely triggered by rapidly rising atmospheric temperatures in early Holocene. Additionally, combining the comprehensive dataset of new radiocarbon ages with 26 radiocarbon ages from previous studies shows a restricted ice sheet extent from 9.1 ± 0.2 to 0.4 ± 0.1 cal ka BP, which coincides with increased sea surface temperatures. Our results highlight past ice sheet sensitivity towards climate changes in one of the least explored and most vulnerable regions of Greenland. Furthermore, comparing our new results to already existing ice sheet models (Huy3 and Huy3b) emphasize the proximal relevance of the Agassiz ice core temperature reconstruction for Melville Bay, which indicates the possible sensitivity of the ice sheet to a warming climate and place improved constraints on ice sheet simulations.