A Japanese piscivorous chub, “hasu” (Opsariichthys uncirostris), and its main prey, “ayu” (Plecoglossus altivelis), both have laterally asymmetric bodies, similar to other fishes; each population consists of righty morphs and lefty morphs. This antisymmetric dimorphism has a genetic basis. Temporal changes in the ratios of laterality (i.e., frequency of righty morphs in a population) of these predator and prey fish species were investigated for a 20-year period at a pelagic site in the southwestern area of Lake Biwa, Japan. The dimorphism of each species was maintained dynamically throughout the period, and the ratio of laterality was found to change periodically in a semi-synchronized manner. Direct inspection of the relationship between the ratios of laterality of the two species indicated that the ratio of ayu followed that of hasu, suggesting that the predator–prey interaction was responsible for the semi-synchronized change. Stomach contents analysis of each hasu revealed that cross-predation, in which righty predators catch lefty prey and lefty predators catch righty prey, occurred more frequently than the reverse combination (parallel-predation). This differential predation is presumed to cause frequency-dependent selection on the two morphs of the predator and prey, and to drive semi-synchronized changes in the laterality of the two species. Some discussion pertaining to the atypical form of the semi-synchronized change in laterality found in this study is presented from the viewpoint of predator–prey interaction in fishes.