The Greenland Ice Sheet has been losing mass at an accelerating rate over the past 2 decades. Understanding ice mass and glacier changes during the preceding several hundred years prior to geodetic measurements is more difficult because evidence of past ice extent in many places was later overridden. Salt marshes provide the only continuous records of relative sea level (RSL) from close to the Greenland Ice Sheet that span the period of time during and since the Little Ice Age (LIA) and can be used to reconstruct ice mass gain and loss over recent centuries. Salt marsh sediments collected at the mouth of Dronning Marie Dal, close to the Greenland Ice Sheet margin in southeastern Greenland, record RSL changes over the past ca. 300 years through changing sediment and diatom stratigraphy. These RSL changes record a combination of processes that are dominated by local and regional changes in Greenland Ice Sheet mass balance during this critical period that spans the maximum of the LIA and 20th-century warming. In the early part of the record (1725–1762 CE) the rate of RSL rise is higher than reconstructed from the closest isolation basin at Timmiarmiut, but between 1762 and 1880 CE the RSL rate is within the error range of the rate of RSL change recorded in the isolation basin. RSL begins to slowly fall around 1880 CE, with a total amount of RSL fall of 0.09±0.1 m in the last 140 years. Modelled RSL, which takes into account contributions from post-LIA Greenland Ice Sheet glacio-isostatic adjustment (GIA), ongoing deglacial GIA, the global non-ice sheet glacial melt fingerprint, contributions from thermosteric effects, the Antarctic mass loss sea level fingerprint and terrestrial water storage, overpredicts the amount of RSL fall since the end of the LIA by at least 0.5 m. The GIA signal caused by post-LIA Greenland Ice Sheet mass loss is by far the largest contributor to this modelled RSL, and error in its calculation has a large impact on RSL predictions at Dronning Marie Dal. We cannot reconcile the modelled RSL and the salt marsh observations, even when moving the termination of the LIA to 1700 CE and reducing the post-LIA Greenland mass loss signal by 30 %, and a “budget residual” of  mm yr−1 since the end of the LIA remains unexplained. This new RSL record backs up other studies that suggest that there are significant regional differences in the timing and magnitude of the response of the Greenland Ice Sheet to the climate shift from the LIA into the 20th century.