Modern deltas are understood to have initiated around 7.5–9 ka in response to the deceleration of sea-level rise. This episode of delta initiation is closely related to the last deglacial meltwater events and eustatic sea-level rises. The initial stage of the Mekong River delta, one of the world's largest deltas, is well recorded in Cambodian lowland sediments. This paper integrates analyses of sedimentary facies, diatom assemblages, and radiocarbon dates for three drill cores from the lowland to demonstrate Holocene sedimentary evolution in relation to sea-level changes. The cores are characterized by a tripartite succession: (1) aggrading flood plain to natural levee and tidal–fluvial channel during the postglacial sea-level rise (10–8.4 ka); (2) aggrading to prograding tidal flats and mangrove forests around and after the maximum flooding of the sea (8.4–6.3 ka); and (3) a prograding fluvial system on the delta plain (6.3 ka to the present). The maximum flooding of the sea occurred at 8.0 ± 0.1 ka, 2000 years before the mid-Holocene sea-level highstand, and tidal flats penetrated up to 20–50 km southeast of Phnom Penh after a period of abrupt ∼5 m sea-level rise at 8.5–8.4 ka. The delta progradation then initiated as a result of the sea-level stillstand at around 8–7.5 ka. Another rapid sea-level rise at 7.5–7 ka allowed thick mangrove peat to be widely deposited in the Cambodian lowland, and the peat accumulation endured until 6.3 ka. Since 6.3 ka, a fluvial system has characterized the delta plain, and the fluvial sediment discharge has contributed to rapid delta progradation. The uppermost part of the sedimentary succession, composed of flood plain to natural-levee sediments, reveals a sudden increase in sediment accumulation over the past 600–1000 years. This increase might reflect an increase in the sediment yield due to human activities in the upper to middle reaches of the Mekong, as with other Asian rivers.