The Greenland ice sheet has been one of the largest contributors to global sea-level rise over the past 20 years, accounting for 0.5 mm yr−1 of a total of 3.2 mm yr−1. A significant portion of this contribution is associated with the speed-up of an increased number of glaciers in southeast and northwest Greenland. Here, we show that the northeast Greenland ice stream, which extends more than 600 km into the interior of the ice sheet, is now undergoing sustained dynamic thinning, linked to regional warming, after more than a quarter of a century of stability. This sector of the Greenland ice sheet is of particular interest, because the drainage basin area covers 16% of the ice sheet (twice that of Jakobshavn Isbræ) and numerical model predictions suggest no significant mass loss for this sector, leading to an under-estimation of future global sea-level rise. The geometry of the bedrock and monotonic trend in glacier speed-up and mass loss suggests that dynamic drawdown of ice in this region will continue in the near future.