Ar-Ar dating of basalt flows capping terrace deposits of the River Euphrates in northern Syria has provided a new quantitative chronology for the late Cenozoic evolution of this important river system and for the associated history of surface uplift of the northern Arabian Platform through which it flows, a region of relatively strong crust that has experienced only slow deformation. Notably, fluvial deposits similar to 65 m above the Euphrates are overlain by basalt dated to 2717 +/- 20 ka, those similar to 45 m above the river are overlain by basalt dated to 2116 +/- 39 ka, and those 8-9 m above the river are overlain by basalt dated to 402 +/- 11 ka. These new dates require the previous dating scheme, based on Paleolithic archaeology, to be revised; the Euphrates terrace deposits and the associated incised valley are much older than was previously thought. Rates of incision by the Euphrates, providing a proxy for regional surface uplift that is inferred to be the isostatic response to regional erosion, have varied significantly over the past similar to 3 Ma, with indications that between similar to 1.2 and similar to 0.9 Ma, there was regional subsidence, which gave rise to fluvial aggradation. This unusual pattern, involving reversals in the sense of vertical crustal motions, is interpreted to be a consequence of a relatively cold and thin mobile lower crustal layer, no more than similar to 5 km thick, evidently due to the presence of a much thicker underlying layer of mafic underplating at the base of the crust. This study thus indicates previously unsuspected complexity in the isostatic response to regional erosion in an area of high crustal stability.