Preserving adaptive capacities of coastal ecosystems, which are currently facing the ongoing climate warming and a multitude of other anthropogenic impacts, requires an understanding of long‐term biotic dynamics in the context of major environmental shifts prior to human disturbances. We quantified responses of nearshore mollusk assemblages to long‐term climate and sea‐level changes using 223 samples (~71,300 specimens) retrieved from latest Quaternary sediment cores of the Adriatic coastal systems. These cores provide a rare chance to study coastal systems that existed during glacial lowstands. The fossil mollusk record indicates that nearshore assemblages of the penultimate interglacial (Late Pleistocene) shifted in their faunal composition during the subsequent ice age, and then reassembled again with the return of interglacial climate in the Holocene. These shifts point to a climate‐driven habitat filtering modulated by dispersal processes. The resilient, rather than persistent or stochastic, response of the mollusk assemblages to long‐term environmental changes over at least 125 thousand years highlights the historically unprecedented nature of the ongoing anthropogenic stressors (e.g., pollution, eutrophication, bottom trawling, and invasive species) that are currently shifting coastal regions into novel system states far outside the range of natural variability archived in the fossil record.