A 7.4 m long sediment core has been retrieved from the central part of Lake Vrana on the island of Cres to reconstruct the paleoenvironmental conditions. Lake Vrana is the deepest freshwater lake in Croatia, located in the karst region of the eastern Adriatic coast. A dated sediment sequence in Lake Vrana of 4.4 m has spanned the past 16.4 kyr, and it featured a dynamic sediment deposition until the beginning of the Holocene, including strong sediment input and supply to the lake by runoff sediments of dolomitic origin from the catchment in the period 16.4–14.4 cal kyr BP. High organic carbon content, which originates from mixed terrestrial and aquatic origins in the periods 14.4–13.3 cal kyr BP and 12.7–11.7 cal kyr BP, indicates fluctuating lake levels in shallow water environments during the Late Glacial to Holocene transition. The Holocene sequence indicates the development of more stable conditions and continuous sediment deposition, characterized by an increasing trend of siliciclastic sediments delivered into the lake during the early Holocene (11.7–10 cal kyr BP) and dominantly from 8 to 4.4 cal kyr BP, indicating enhanced input and erosion, which coincides with the humid and pluvial period recorded in the central Mediterranean region. It is followed by sediments with high organic carbon content between 4.4 and 1.6 cal kyr BP, which points to higher lake productivity. Calcite sedimentation prevailed between 1.6 to 0.4 cal kyr BP, indicating stable deeper-lake conditions. Predominantly, siliciclastic sediments from 0.4 to 0.1 cal kyr BP pointed to erosion during the Little Ice Age (LIA), with enhanced precipitation and sediment discharge from the catchment. The re-establishment of calcite sedimentation has been observed over the last 100 years.