Nhecolândia is a fossil lobe of the Taquari River megafan and a prominent geomorphic subunit of the Pantanal wetlands because of the presence of >10,000 small lakes. We investigated the stratigraphic records of three saline lakes from Nhecolândia to explore their potential as Quaternary hydroclimate archives. Radiocarbon data indicate that accumulation at two lakes was approximately continuous in the late Holocene, and chemostratigraphic variability suggests sensitivity to environmental change with multicentennial resolution. A basal sandy unit and an upper muddy unit comprise the shallow stratigraphy of each lake. A pronounced change in depositional environment from freshwater wetlands to saline lakes at ~3300–3200 cal yr BP best explains the lithofacies transition. Ephemeral freshwater wetlands formed on the abandoned megafan lobe, which was molded by deflation in the arid early Holocene. Wind-scouring of the megafan lobe generated topographically closed depressions with complex marginal sand ridges, which allowed permanent lakes to evolve when rainfall increased in the late Holocene. The lakes became highly saline and alkaline after ~910 cal yr BP, which influences biogeochemistry and aquatic ecology. The results hold implications for understanding the response of the southern Pantanal to climate change, as well as the development of pans in tropical megafan settings.