Predation is an important driver of species-level change in modern and fossil ecosystems, often through selection for defensive phenotypes in prey responding to predation pressures over time.1–8 Records of changes in shell morphology and injury patterns in biomineralized taxa are ideal for demonstrating such adaptive responses.9–11 The rapid increase in diversity and abundance of biomineralizing organisms during the early Cambrian is often attributed to predation and an evolutionary arms race.12–27 A Cambrian arms race is typically discussed on a macroevolutionary scale, particularly in the context of escalation.12,27–29 Despite abundant fossils demonstrating early Cambrian predation, empirical evidence of adaptive responses to predations is lacking. To explore the Cambrian arms race hypothesis, we assessed a large sample of organophosphatic sclerites of the tommotiid Lapworthella fasciculata from a lower Cambrian carbonate succession in South Australia,30–32 >200 of which show holes made by a perforating predator.33,34 Critically, the frequency of perforated sclerites increases over time, with a combination of time-series analyses and generalized linear models suggesting a positive correlation with sclerite thickness. These observations reflect a population-level adaptive response in L. fasciculata and the oldest known microevolutionary arms race between predator and prey. Propagation of such interactions across early Cambrian ecosystems likely resulted in the proliferation of biomineralizing taxa with enhanced defenses, illustrating the importance of predation as a major ecological driver of early animal evolution.12,14,20,35