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ABSTRACT Tropical reef ecosystems are strongly influenced by the composition of coral species, but the factors influencing coral diversity and distributions are not fully understood. Here we demonstrate that large variations in the relative abundance of three major coral species across adjacent Caribbean reef sites are strongly related to their different low O₂tolerances. In laboratory experiments designed to mimic reef conditions, the cumulative effect of repeated nightly low O₂drove coral bleaching and mortality, with limited modulation by temperature. After four nights of repeated low O₂, species responses also varied widely, from > 50% bleaching inAcropora cervicornisto no discernable sensitivity ofPorites furcata.A simple metric of hypoxic pressure that combines these experimentally derived species sensitivities with high‐resolution field data accurately predicts the observed relative abundance of species across three reefs. Only the well‐oxygenated reef supported the framework‐building hypoxia‐sensitiveAcropora cervicornis, while the hypoxia‐tolerant weedy speciesPorites furcatawas dominant on the most frequently O₂‐deplete reef. Physiological exclusion of acroporids from these O₂‐deplete reefs underscores the need for hypoxia management to reduce extirpation risk.