The Holocene sediment record of Lake Tiefer See exhibits striking alternations between well-varved and non-varved intervals. Here, we present a high-resolution multi-proxy record for the past ~6000 years and discuss possible causes for the observed sediment variability. This approach comprises microfacies, geochemical and microfossil analyses and a multiple dating concept including varve counting, tephrochronology and radiocarbon dating. Four periods of predominantly well-varved sediment were identified at 6000–3950, 3100–2850 and 2100–750 cal. a BP and AD 1924–present. Except of sub-recent varve formation, these periods are considered to reflect reduced lake circulation and consequently, stronger anoxic bottom water conditions. In contrast, intercalated intervals of poor varve preservation or even extensively mixed non-varved sediments indicate strengthened lake circulation. Sub-recent varve formation since AD 1924 is, in addition to natural forcing, influenced by enhanced lake productivity due to modern anthropogenic eutrophication. The general increase in periods of intensified lake circulation in Lake Tiefer See since ~4000 cal. a BP presumably is caused by gradual changes in the northern hemisphere orbital forcing, leading to cooler and windier conditions in Central Europe. Superimposed decadal- to centennial-scale variability of the lake circulation regime is likely the result of additional human-induced changes of the catchment vegetation. The coincidence of major non-varved periods at Lake Tiefer See and intervals of bioturbated sediments in the Baltic Sea implies a broader regional significance of our findings.