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Our study uses data from Holocene core samples and modern death assemblages to understand how human-induced environmental change in the northern Adriatic Sea (Italy) may have affected parasite-host dynamics in the economically important bivalve Chamelea gallina. Thirty-one radiocarbon dates confirm temporal distinctness between the periods before and after the onset of significant human influence and confirm that trematode prevalence has decreased by an order of magnitude over the past ∼2 k.y. The median number of parasite-induced pits per bivalve host and parasite aggregation has also decreased significantly, signaling a substantial decrease in the effective population size of digenean trematodes. Gaussian finite mixture modeling of pit size does not support the hypothesis of parasite extinction. Combined, these results indicate the (potentially ongoing) collapse of parasite-host interactions in C. gallina in concert with human influence on the Adriatic and its transition to an urban sea.