Over the past two decades, ice loss from the Greenland ice sheet (GrIS) has increased owing to enhanced surface melting and ice discharge to the ocean^1–5. Whether continuing increased ice loss will accelerate further, and by how much, remains contentious^6–9. A main contributor to future ice loss is the Northeast Greenland Ice Stream (NEGIS), Greenland’s largest basin and a prominent feature of fast-flowing ice that reaches the interior of the GrIS^10–12. Owing to its topographic setting, this sector is vulnerable to rapid retreat, leading to unstable conditions similar to those in the marine-based setting of ice streams in Antarctica^13–20. Here we show that extensive speed-up and thinning triggered by frontal changes in 2012 have already propagated more than 200 km inland. We use unique global navigation satellite system (GNSS) observations, combined with surface elevation changes and surface speeds obtained from satellite data, to select the correct basal conditions to be used in ice flow numerical models, which we then use for future simulations. Our model results indicate that this marine-based sector alone will contribute 13.5–15.5 mm sea-level rise by 2100 (equivalent to the contribution of the entire ice sheet over the past 50 years) and will cause precipitous changes in the coming century. This study shows that measurements of subtle changes in the ice speed and elevation inland help to constrain numerical models of the future mass balance and higher-end projections show better agreement with observations.