Host dispersal is now recognized as a key predictor of the landscape-level persistence and expansion of parasites. However, current theories treat post-infection dispersal propensities as a fixed trait, and the plastic nature of host’s responses to parasite infection has long been underappreciated. Here, we present a mark-recapture experiment in a single-host parasite system (larval parasites of the freshwater mussel Margaritifera laevis and its salmonid fish host Oncorhynchus masou masou) and provide the first empirical evidence that parasite infection induces size-dependent host dispersal in the field. In response to parasite infection, large fish become more dispersive, whereas small fish tend to stay at the home patch. The observed plasticity in dispersal is interpretable from the viewpoint of host fitness: expected benefits (release from further infection) may exceed dispersal-associated costs for individuals with high dispersal ability (i.e., large fish) but are marginal for individuals with limited dispersal ability (i.e., small fish). Indeed, our growth analysis revealed that only small fish hosts incurred dispersal costs (reduced growth). Strikingly, our simulation study revealed that this plastic dispersal response of infected hosts substantially enhanced parasite persistence and occupancy in a spatially structured system. These results suggest that dispersal plasticity in host species is critical for understanding how parasites emerge, spatially spread, and persist in nature. Our findings provide a novel starting point for building a reliable, predictive model for parasite/disease management.