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Abstract Global ocean oxygen loss is projected to persist in the future, but Earth system models (ESMs) have not yet provided a consistent picture of how it will influence the largest oxygen minimum zone (OMZ) in the tropical Pacific. We examine the change in the Pacific OMZ volume in an ensemble of ESMs from the CMIP6 archive, considering a broad range of oxygen (O2) thresholds relevant to biogeochemical cycles and ecosystems (5–160 µmol/kg). Despite OMZ biases in the historical period of the simulations, the ESM ensemble projections consistently fall into three regimes across ESMs: an expansion of low oxygenated waters (+0.8 [0.6, 1.0] × 1016 m3/century for O2 ≤ 120 µmol/kg, ESM median and interquartile range); a slight contraction of the OMZ core although more uncertain across ESMs (−0.1 [−0.5, 0.0] × 1016 m3/century for O2 ≤ 20 µmol/kg); and at the transition from contraction to expansion regimes, a spatial redistribution but near‐zero change in the volume of hypoxic waters (0.0 [−0.3, +0.1] × 1016 m3/century for O2 ≤ 60 µmol/kg). Changes in circulation and biology dictate the shift from expansion to contraction. Specifically, reduced subtropical ventilation controls the expansion of low oxygenated waters, while a combination of circulation and biological changes explains the contraction of the core (likely changes in mixing, reduced intermediate ventilation and oxygen demand). Increased model complexity (e.g., ecosystem dynamics and equatorial circulation) likely stabilize the OMZ response, suggesting that future changes might lie in the lower bound of current projections. The expansion of low oxygenated waters which delimit the optimum habitat of numerous marine species would severely impact ecosystems and ecosystem services.