The eastern Acheloos River delta and the Lagoon of Etoliko have undergone broad environmental changes since the mid-Holocene. In this study, sedimentological, geochemical, geophysical, micromorphological, computer tomographical, micro- and macrofaunal, and archaeobotanical methods were applied to determine lateral and vertical facies patterns of near-coast geological archives. We present the stratigraphic sequences of 13 vibracores and one 9-m-long sediment core from the Lagoon of Etoliko. Geochronology was based on 28 radiocarbon dates. Sea-level fluctuations were detected by means of sedimentological sea-level markers. The relative sea level rose from 12.70 m below sea level (b.s.l.) at 6150 cal BC to 7.90 m b.s.l. by 4750 cal BC and 2.60 m b.s.l. by 500 cal BC. The maximum rate of rise occurred until 5550 cal BC, and the lowest, between Helladic and Byzantine times. Delta growth clearly increased after the relative sea-level rise decelerated around 5500 cal BC. Palaeogeographical maps for different points in time are presented here. During the Last Glacial Maximum, a freshwater lake existed in the Etoliko basin. At 4750 cal BC, the Acheloos River delta had already crossed the Paracheloïtis lowland pass and prograded into the Lagoon of Mesolongion, which was closed off from the sea by a barrier system. At 3600 cal BC, a distributary broke into the Lake of Etoliko. Progradation of a large deltaic plain toward the southeast took place until 1550 cal BC. Then, direct river water inflow into the Lake of Etoliko ceased. Circa 1200 cal BC, the river was definitely redirected toward the western part of the delta, and ongoing relative sea-level rise, possibly associated with coastal erosion, connected the Lake of Etoliko to the Lagoon of Mesolongion. Since then, the delta plain has undergone further submergence. Geoarchaeological aspects are also discussed with regard to the palaeogeographical evolution of the area.