We sampled modern chironomids at multiple water depths in Lake Annecy, France, before reconstructing changes in chironomid assemblages at sub-decadal resolution in sediment cores spanning the last 150 years. The lake is a large, deep (z(max) = 65 m), subalpine waterbody that has recently returned to an oligotrophic state. Comparison between the water-depth distributions of living chironomid larvae and subfossil head capsules (HC) along three surface-sediment transects indicated spatial differences in the influence of external forcings on HC deposition (e.g. tributary effects). The transect with the lowest littoral influence and the best-preserved, depth-specific chironomid community characteristics was used for paleolimnological reconstructions at various water depths. At the beginning of the twentieth century, oxygen-rich conditions prevailed in the lake, as inferred from M. contracta-type and Procladius sp. at deep-water sites (i.e. cores from 56 to 65 m) and Paracladius sp. and H. grimshawi-type in the core from 30 m depth. Over time, chironomid assemblages in cores from all three water depths converged toward the dominance of S. coracina-type, indicating enhanced hypoxia. The initial change in chironomid assemblages from the deep-water cores occurred in the 1930s, at the same time that an increase in lake trophic state is inferred from an increase in total organic carbon (TOC) concentration in the sediment. In the 1950s, an assemblage change in the core from 30 m water depth reflects the rapid expansion of the hypoxic layer into the shallower region of the lake. Lake Annecy recovered its oligotrophic state in the 1990s. Chironomid assemblages, however, still indicate hypoxic conditions, suggesting that modern chironomid assemblages in Lake Annecy are decoupled from the lake trophic state. Recent increases in both TOC and the hydrogen index indicate that changes in pelagic functioning have had a strong indirect influence on the composition of the chironomid assemblage. Finally, the dramatic decrease in HC accumulation rate over time suggests that hypoxic conditions are maintained through a feedback loop, wherein the accumulation of (un-consumed) organic matter and subsequent bacterial respiration prevent chironomid re-colonization. We recommend study of sediment cores from multiple water depths, as opposed to investigation of only a single core from the deepest part of the lake, to assess the details of past ecological changes in large deep lakes.