The Vietnamese Mekong Delta was formed by rapid transgression during the second half of the Holocene by deposition of mainly unconsolidated, fine-grained (clayey) sediments undergoing high compaction rates. The natural subsidence can seriously impact the already vulnerable delta plain as its low elevation exposes the delta to global sea level rise, flooding, salinization. Human activities such as groundwater pumping, infrastructural loading, sand mining and dam construction have exacerbated the effects of natural consolidation. Here we present a novel modeling study that has allowed to reproduce the formation and evolution of the Mekong delta over the past 4000 years. Using an adaptive finite-element mesh, the model properly simulates accretion and natural consolidation characterizing the delta evolution. Large soil grain motion and the delayed dissipation of pore-water overpressure are accounted for. We find that natural compaction of Holocene deposits following delta evolution exceeds predicted values of absolute sea level rise. The unprecedented high rates (up to ~20 mm/yr) threaten the lower delta plain with permanent inundation and inevitably reduce the designed service life of flood defense structures along the coast. Total subsidence and sediment delivery to the delta plain will determine its future elevation and vulnerability to relative sea level rise.