Lakes are threatened by contemporary climate change and human activities. Paleohydrological records provide important evidence for developing scenarios for future changes in the availability of freshwater resources. This study presents a synthesis of a sedimentological, archeological, and chronological dataset collected from Lake Annecy (eastern France) to reconstruct a lake-level record documenting the whole Holocene. This dataset shows a pronounced minimum in the lake level during the Holocene thermal maximum (HTM) (ca. 9000–7000 cal BP), preceded by a general lowering trend (early Holocene), and followed by a general rising trend (Neoglacial). On both the millennial and centennial scales, the Lake Annecy record appears to match the regional pattern of Holocene lake-level fluctuations established for West-Central Europe. In agreement with other extra-regional paleoclimatic records, it shows the dominant influence of orbital forcing. The high magnitude of the lake-level lowering (more than 5 m) during the HTM, with a 2–2.5 °C difference between the HTM and the pre-industrial mean summer temperatures, suggests possible drastic lake-level lowering phases in the near future depending on the IPCC scenarios following climate change. This would mean dramatic impacts on human activities and the preservation of exceptional archeological remains in regional lake basins.