Understanding the influence of natural climatic variability on modern fisheries is complicated by over a century of industrial fishing. Archaeological data provide unique opportunities for assessing precolonial and preindustrial fisheries. Records show that anchoveta-vs sardine-dominated fisheries correlate with 20th-century climate change in the Pacific Basin and are linked to multidecadal climatic variability. The “anchovy regime” is characterized by cooler conditions and lower frequency El Niño/Southern Oscillation (ENSO) events, while the “sardine regime” is associated with warmer conditions and higher frequency ENSO. Fish remains excavated at Lo Demás, an Inca-period (ca. A.D. 1480–1540) fishing site at 13°25′S on the Peruvian coast, document a shift from an anchoveta-to a sardine-dominated fishery at about A.D. 1500. This shift correlates with records for increasing ENSO frequency at the same time. Middle and late Holocene sites have archaeofish assemblages that also suggest regime changes. Here we show that changes in fish regimes can result from natural variability and we support the potential role of archaeological assemblages in tracking multidecadal climate change in the Pacific Basin throughout the Holocene (0–11,500 cal yr B.P.).