Anomalocardia flexuosa is a bivalve that inhabits shallow, low hydrodynamics coastal environments of normal to brackish salinity, currently distributed from the Caribbean up to the state of Santa Catarina (∼28°S) in southern Brazil, but its fossil record extends along the southwestern Atlantic up to ∼40°S, in Argentina. Its absence in southern coasts today is attributed to ocean water cooling as a result of Middle-Late Holocene changes in relative influence of the warm waters of the Brazil Current and the cold waters of the Malvinas/Falklands Current, but geomorphologic and stratigraphic data suggest that coastal evolution controlled mainly by glacioeustatic-driven oscillations may have also played a role on the shifts of its distribution. Here we review the past and present distribution of A. flexuosa along southern Brazil, establishing a correlation with the Holocene geological history of this area. The Holocene post glacial marine transgression (PMT) produced a large complex of interconnected coastal lagoons landward of sandy barriers stretching from southern Brazil (state of Rio Grande do Sul) to Argentina, creating a corridor that allowed for the southward dispersion of A. flexuosa. The few available numerical ages indicate that A. flexuosa was established in the northern coastal plain of Rio Grande do Sul around ∼7.1 ka BP, and by ∼5.8 ka BP it had reached the southern plain, facilitated by warmer ocean waters than today and the sea-level highstand of 6–5 ka BP. The combination of cooling, sea-level fall that reduced marine influence, and fluvial inputs of freshwater and sediments, converted most of the lagoon complex into smaller isolated freshwater lakes after ∼4 ka BP, leading to the regional extinction of that species. The fossils of A. flexuosa and other tropical mollusks in middle and late Pleistocene interglacial barrier-lagoon coastal deposits along the southwestern Atlantic suggest that their latitudinal distribution shifted cyclically, driven by glacial-interglacial oscillations of sea-level and temperatures. The understanding of the coastal processes that affected the distribution of A. flexuosa may help assessing how mollusks and other marine species respond to environmental forcings related to sea-level oscillations and climate, thus contributing from a paleobiological perspective for conservation and management efforts under present and future scenarios of changes in coastal ecosystems.