Global ocean oxygen loss - deoxygenation - is projected to persist in the future. Previous generations of Earth system models (ESMs) have, however, failed to provide a consistent picture of how deoxygenation will influence oxygen minimum zones (OMZs; O2<= 80 μmol/kg), in particular the largest OMZ in the tropical Pacific Ocean. The expansion of the Pacific OMZ would threaten marine ecosystems and ecosystem services such as fisheries and could amplify climate change by emitting greenhouse gases. Here, we use the latest generation of ESMs (CMIP6) and a density framework that isolates oxygen changes in the thermocline and intermediate waters. We show that the Pacific OMZ expands by the end of the century in response to high anthropogenic emissions (multi-ESM median expansion of 2.4 * 10^15 m^3m, about 4% of the observed OMZ volume). The expansion is driven by a reduction of the shallow overturning circulation in the thermocline and a robust weakening of the oxygen supply to the upper OMZ in all ESMs. The magnitude of this expansion is, however, uncertain due to the less constrained balance between physical and biological changes in the lower OMZ. Despite uncertainties in the biological response, our results suggest that models with more complex biogeochemistry project weaker changes in the lower OMZ, and therefore stronger overall OMZ expansion. The fact that the OMZ largely expands in the upper ocean maximizes its ecological, economic, and climatic impacts (release of greenhouse gases).