Climate and sea-level changes strongly controlled the evolution of shallow coastal settings worldwide during the Quaternary Period. The shallow coastal region has been subjected to repeated alternations between the subaerial and marine conditions. The Krka River mouth area located in central Dalmatia along the microtidal Eastern Adriatic coast represents a suitable environmental setting for studying palaeoenvironments and relative sea-level changes. An evolutionary model of the Krka River coastal depositional system was reconstructed by combining high-resolution acoustic methods and a multiproxy analysis of sediment cores. The acoustic methods (bathymetrical and seismic studies) provided insight into the submerged geomorphology and up to 30 m thick sediment sequences preserved in the study area. The multiproxy analysis was conducted on six sediment cores and included physical, sedimentological, geochemical, and micropalaeontological analyses supported by 24 radiocarbon dates (14C) to obtain data on benthic communities, hydrological, and depositional processes related to sea level and climatic conditions and timing of events. The results indicated fluvial incision and sediment bypass towards the shelf area during the period of low sea level (lowstand), whereas during the transgressive phase, the shelf area and subsequently the River canyon were flooded. A system of calcareous tufa barriers started to form in the upstream tract of the recent Krka River estuary. The calcareous tufa barrier system, together with sea-level and climate oscillations, had the main influence on the palaeoenvironmental development of the area. The Holocene sea-level rise progressively flooded the tufa barriers with the formation of estuarine conditions during the Late Holocene. Human activity intensified after 600 cal yr BP.