The aim of this study is to provide new data on relative sea-level changes and neotectonics of the northeastern Aegean Sea region (Eastern Mediterranean) through the analysis of the coastal geomorphology of Lesvos, the third largest Greek island. There is a paucity of presently available data in this sector of the Aegean Sea, which is a tectonically active area strongly controlled by the North Anatolian Fault. In this paper, morphological, biological and sedimentary records of paleo-sea levels have been used to reconstruct relative sea-level changes, to identify variations in the tectonic regimes as well as to assess the paleoseismicity in the studied areas. According to the results, late Quaternary relative sea-level changes at Lesvos were not homogenous and variations in the tectonic setting played a crucial role in the coastal evolution. The NW-SE trending faults on the southern shore of the island control a significant uplift affecting about 30 km of coastline. This uplift trend is controlled by the footwall of the Lesvos Fault, a major offshore normal fault that has been subject to relatively little quantitative investigation. Radiocarbon dating indicated that the last co-seismic uplift took place at 3365-3963 cal yr BP and resulted in about 0.75 m of vertical displacement. In contrast, all the paleo-sea-level markers mapped in the northeastern sector were presently underwater and, despite the high seismicity of the area, no evidence of coastal uplift was observed in this part of the island. Thus, the paper provides the first field evidence of a differential late Quaternary evolution of Lesvos Island. In addition, results represent the first quantitative information on the activity of the Lesvos Fault, suggesting a reconsideration of its importance in the neotectonics of the area.