The Tonle Sap, the 'Great Lake' of central Cambodia, is the central component of wetland ecosystems in the lower Mekong River basin, and is of enormous conservation value. The lake's unusual hydraulic relationship with the Mekong River, and its consequent sensitivity to monsoon variability, makes the Tonle Sap sensitive to climate change. Exploring the dynamics and development of this system under different climate regimes of the past offers a perspective on possible future impacts, which is critical for sound management. Biostratigraphic and sedimentological data derived from cores of lake sediment indicate that during the period >7000 to ca. 5500 14C years Before Present the lake was less variable than present in terms of depth during the annual cycle of flood, and may have been strongly influenced by saline tidal waters associated with higher-than-present seas levels. As regional environments became drier and more seasonal in the late Holocene, more sediment was re-suspended during the increasingly marked dry season lake level minimum, lowering the effective sediment accumulation rate. Contrary to current interpretations of the history of the lake and associated wetland ecosystems, the data presented here imply that regional hydraulic connections between the lake and the Mekong River existed from at least the early Holocene.