Nioghalvfjerdsfjorden is a major outlet glacier in Northeast-Greenland. Although earlier studies showed that the floating part near the grounding line thinned by 30% between 1999 and 2014, the temporal ice loss evolution, its relation to external forcing and the implications for the grounded ice sheet remain largely unclear. By combining observations of surface features, ice thickness and bedrock data, we find that the ice shelf mass balance has been out of equilibrium since 2001, with large variations of the thinning rates on annual/multiannual time scales. Changes in ice flux and surface ablation are too small to produce this variability. An increased ocean heat flux is the most plausible cause of the observed thinning. For sustained environmental conditions, the ice shelf will lose large parts of its area within a few decades and ice modeling shows a significant, but locally restricted thinning upstream of the grounding line in response.