A lake-level record of Lake Ledro (northern Italy) spans the entire Holocene with a chronology derived from 51 radiocarbon dates. It is based on a specific sedimentological approach that combines data from five sediment profiles sampled in distinct locations in the littoral zone. On a millennial scale, the lake-level record shows two successive periods from 11,700 to 4500 cal yr BP and from 4500 cal yr BP to the present, characterized by lower and higher average lake levels, respectively. In addition to key seasonal and inter-hemispherical changes in insolation, the major hydrological change around 4500 cal yr BP may be related to a non-linear response of the climate system to orbitally-driven gradual decrease in insolation. The Ledro record questions the notion of an accentuated summer rain regime in the northern Mediterranean borderlands during the boreal insolation maximum. Moreover, the Ledro record highlights that the Holocene was punctuated by successive centennial-scale highstands. Correlations with the Preboreal oscillation and the 8.2 ka event, and comparison with the atmospheric 14C residual record, suggest that short-lived lake-level fluctuations developed at Ledro in response to (1) final steps of the deglaciation in the North Atlantic area and (2) variations in solar activity.