The role of antagonistic organismal interactions in the production of long-term macroevolutionary trends has been debated for decades. Some evidence seems to suggest that temporal trends in predation frequency share a common causative mechanism with genus-level diversity, whereas studies on the role of parasites in “shaping” the evolutionary process are rare indeed. Digenean trematodes (Phylum Platyhelminthes) infest molluscs in at least one stage of their complex life cycle. Trematodes leave characteristic oval-shaped pits with raised rims on the interior of their bivalve hosts, and these pits are preserved in the fossil record. Here we survey 11,785 valves from the Pleistocene–Holocene deposits of the Po Plain and from nearby modern coastal environments on the northeast Adriatic coast of Italy. Of these, 205 valves exhibited trematode-induced pits. Trematodes were selective parasites in terms of host taxonomy and host body size. Infestation was restricted to lower shoreface/transition-to-platform paleoenvironments. During the Holocene, individuals from the transgressive systems tract were significantly more likely to be infested than those from highstand systems tracts. Temporal trends in infestation frequency cannot be explained as an ecological/evolutionary phenomenon (e.g., the hypothesis of escalation); instead the trend seems controlled by environmental variation induced by glacio-eustatic sea-level changes and inadequate sampling. Because this interaction appears to be ephemeral, both temporally and spatially, it is not likely that any selective pressure would be continuous over geologic time in this region. Furthermore, these results support the hypothesis that antagonistic interactions are lower in the northern Adriatic Sea in comparison to other midlatitude shallow marine settings.