The spatiotemporal distribution of biochemical varves spanning the last 150 yr was investigated using 40 cores collected over a depth gradient in a large subalpine lake-Lake Bourget-in the French Alps. Four-dimensional sedimentological, biological, and geochemical analyses show that varve preservation can be used as a reliable proxy to reconstruct annual-to-decadal oscillations of hypoxia in large lakes. The volume of hypoxic waters was calculated by integrating the volume between the lake bottom and the depth of the shallowest varve-bearing core for each year. Although Lake Bourget bottom waters have been oxic over the last 9000 yr, severe hypoxia has occurred only since 193361. The volume of hypoxic waters showed, thereafter, a succession of pronounced fluctuations, leading to an increase of 8% of the total lake volume in the 1960s, a decline in the 1980s, and a second, ongoing increase since 1990. Whereas the initial onset of persistent hypoxic conditions could be attributed to eutrophication due to nutrient-rich inputs from sewage water and/or diffuse contamination, the later fluctuations were also driven by climatic factors, i.e., flooding, rising air temperatures, and phosphorus-independent changes in primary production. Hence, cumulative effects related to global warming seem to have driven hypolimnetic hypoxic conditions since equilibrium was initially disrupted due to a drastic shift in the trophic state.