The sensitivity of the Northeast Greenland Ice Stream (NEGIS) to prolonged warm periods is largely unknown and geological records documenting such long-term changes are needed to place current observations in perspective. Here we use cosmogenic surface exposure and radiocarbon ages to determine the magnitude of NEGIS margin fluctuations over the last 45 kyr (thousand years). We find that the NEGIS experienced slow early Holocene ice-margin retreat of 30-40 m a-1, likely as a result of the buttressing effect of sea-ice or shelf-ice. The NEGIS was 20-70 km behind its present ice-extent 41-26 ka and 7.8-1.2 ka; both periods of high orbital precession index and/or summer temperatures within the projected warming for the end of this century. We show that the NEGIS was smaller than present for approximately half of the last 45 kyr and is susceptible to subtle changes in climate, which has implications for future stability of this ice stream.