The mesopelagic (200-1000 m) separates the productive upper ocean from the deep ocean, yet little is known of its long-term dynamics despite recent research that suggests fishes of this zone likely dominate global fish biomass and contribute to the downward flux of carbon. Here we show that mesopelagic fishes dominate the otolith (ear bone) record in anoxic sediment layers of the Santa Barbara Basin over the past two millennia. Among these mesopelagic fishes, otoliths from families Bathylagidae (deep-sea smelts) and Myctophidae (lanternfish) are most abundant. Otolith deposition rate fluctuates at decadal to centennial time scales and covaries with proxies for upper ocean temperature, consistent with climate forcing. Moreover, otolith deposition rate and proxies for temperature and primary productivity show contemporaneous discontinuities during the Medieval Climate Anomaly and Little Ice Age. Mesopelagic fishes may serve as proxies for future climatic influence at those depths including effects on the carbon cycle.