The finely laminated sediment record of a permanent, hypersaline, desert oasis lake in the Ounianga region of northeastern Chad presents a unique opportunity to document the hydrological evolution of this groundwater-fed aquatic ecosystem during mid- and late-Holocene desiccation of the Sahara. In this study we reconstruct long-term changes in zoobenthos and zooplankton communities of Lake Yoa as their early-Holocene freshwater habitat changed into the hypersaline conditions prevailing today. Chironomid production peaked during the fresh-to-saline transition period, then stabilized at about half that of the earlier freshwater ecosystem. Quantitative salinity inferences based on fossil chironomid assemblages indicate that the fresh-to-saline transition occurred fairly abruptly between ∼4100 and 3400 cal yr BP, but that the ecosystem was buffered against shorter-term climate fluctuations due to continuous inflow of fossil groundwater. The mixture of tropical-African and southern Palaearctic chironomid faunas in the Lake Yoa fossil record required us to address several methodological issues concerning chironomid-based salinity reconstruction, and the applicability of a calibration dataset based on tropical East and West African lakes to this Sahara desert locality. The most coherent reconstruction was obtained with an inference model that applies a weighted best-modern-analogue (WMAT) transfer function to the African calibration dataset expanded with six Sahara lakes.