The history of variations in water level of Lake Constance, as reconstructed from sediment and pollen analysis of a sediment sequence from the archaeological site of Arbon-Bleiche 3, shows an abrupt rise in lake level dendrochronologically dated to 5375 yr ago (5320 yr relative to AD 1950). This event, paralleled by the destruction of the Neolithic village by fire, provoked the abandonment of this prehistoric lake-shore location established in the former shallow bay of Arbon-Bleiche, and was the last of a series of three episodes of successively higher lake level, the first occurring at 5600–5500 cal yr B.P. The dendrochronologically dated rise event was synchronous with an abrupt increase in atmospheric 14C. This supports the hypothesis of an abrupt climate change forced by varying solar activity. Moreover, the three successive episodes of higher lake level between 5600 and 5300 cal yr B.P. at Arbon-Bleiche 3 coincided with climatic cooling and/or changes in moisture conditions in various regions of both hemispheres. This period corresponds to the mid-Holocene climate transition (onset of the Neoglaciation) and suggests inter-hemispheric linkages for the climate variations recorded at Arbon-Bleiche 3. This mid-Holocene climate reversal may have resulted from complex interactions between changes in orbital forcing, ocean circulation and solar activity. Finally, despite different seasonal hydrological regimes, the similarities between lake-level records from Lake Constance and from Jurassian lakes over the mid-Holocene period point to time scale as a crucial factor in considering the possible impact of climate change on environments.