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Abstract A high-resolution sedimentological and geochemical analysis of a 21 m sediment sequence of Lake Iseo (Southern Alps, Italy) allowed for the reconstruction of the long-term flood frequency by visual identification of the event layers over the last 12 kyr cal BP. In a previous study that was undertaken on another sediment core from Lake Iseo, these layers were attributed to extreme surface runoff events. However, in this former core, large mass-wasting deposits that induce significant hiatuses did not permit a continuous record of flood events to be established. Such disturbances were absent in the core studied in the present paper. This permitted to establish a high-resolution continuous Holocene record. Based on the flood chronicle and sedimentological and XRF geochemical analyses, we found evidence of a major palaeohydrological transition at approximately 3.8 kyr cal BP, which was previously described as occurring in the western Mediterranean region. The oldest part of the record indeed presents a very low frequency of flood events (<1 flood/century), while after 4 kyr cal BP, the flood frequency increased. This pattern appears to be in agreement with other Southern Alpine paleo flood records. The transition is interpreted as a nonlinear climate response to the orbital-driven gradual decrease in summer insolation at 60°N, which together with the influence of the Mediterranean mesoscale precipitation events, is typical for the Mediterranean climate. However, the comparison of the flood record with the archaeological and historical data from the watershed suggests that human activity during the Roman period in the vicinity of the main tributaries also influenced the flood frequency. Even in a large Alpine lake and >2000 years ago, extreme precipitation events that were recorded through the sedimentation process can hence be impacted by the anthropization of the catchment area pointing the requirement of deeper studies of Earth surface critical zone pluri-millennial dynamics. Highlights • In the Alps, flood frequency is higher during period of cold and wetter climate. • A major palaeohydrological transition is observed at approximately 4 kyr cal BP. • From 2 kyr cal BP, human activity is the main driver of the SEB10 flood frequency. • In Alpine lowland lake, flood chronicle can be impacted by the anthropization. • Studying human activity is needed for flood-paleohydrological reconstructions. [ABSTRACT FROM AUTHOR]