The nature of the southern margin of the Anatolian microplate during the Neogene is complex, controversial and fundamental in understanding active plate-margin tectonics and natural hazards in the Eastern Mediterranean region. Our investigation provides new insights into the Late Pleistocene uplift history of Cyprus and the Troodos Ophiolite. We provide isotopic (14C) and radiogenic (luminescence) dates of outcropping marine sediments in eastern Cyprus that identify periods of deposition during marine isotope stages (MIS) 3, 4, 5 and 6. Past sea-levels indicated by these deposits are c. 95±25 m higher in elevation than estimates of worldwide eustatic sea-level. An uplift rate of c. 1.8 mm/year and possibly as much as c. 4.1 mm/year in the past c. 26–40 ka is indicated. Holocene marine deposits also occur at elevations higher than those expected for past SL and suggest uplift rates of c. 1.2–2.1 mm/year. MIS-3 marine deposits that crop out in southern and western Cyprus indicate uniform island-wide uplift. We propose a model of tectonic wedging at a plate-bounding restraining bend as a mechanism for Late Pleistocene to Holocene uplift of Cyprus; uplift is accommodated by deformation and seismicity along the margins of the Troodos Ophiolite and re-activation of its low-angle, basal shear zone.