Two sediment cores collected from the saline lagoon St. Michiel on Curaçao (Dutch Antilles) preserve a ~5000-yr record of environmental change. Investigation of radiocarbon-dated sections by accelerator mass spectrometry (AMS) is based on faunal assemblage analyses, sediment mineralogy, and the interpretation of sedimentary facies. The cores recovered from different parts of the lagoon demonstrate different development. Initially, in the proximal part of the lagoon (core STM-2), the sediment accumulated in a coastal, semi-protected bay with strong marine influence, whereas the distal part (STM-1) was dominated by chemical precipitation (gypsum, aragonite). By about 3500–3400 BP, connection with the open sea became very limited due to the gradual formation of a coral rubble barrier at the coastline. Subsequently, the record reveals undisturbed sedimentation in the highly restricted shallow lagoon. Around 1100–1000 BP, biological and sedimentological records indicate a change to less evaporitic conditions. Stages of increased salinity are intercalated with intervals of episodic freshening due to increased runoff and precipitation. The authors demonstrate that since permanent human settlements were established on the island about 1100 BP, the watershed has undergone intensive deforestation, especially during the European colonization at the beginning of the 16th century. Deforestation resulting from agriculture and construction caused increased erosion, which was translated to increased sediment accumulation rates and a shift in lagoon sedimentation from almost entirely endogenic to mostly detrital.