Climate warming is expected to reduce oxygen (O2) supply to the ocean and expand its oxygen minimum zones (OMZs). We reconstructed variations in the extent of North Pacific anoxia since 1850 using a geochemical proxy for denitrification (δ15N) from multiple sediment cores. Increasing δ15N since ~1990 records an expansion of anoxia, consistent with observed O2 trends. However, this was preceded by a longer declining δ15N trend that implies that the anoxic zone was shrinking for most of the 20th century. Both periods can be explained by changes in winds over the tropical Pacific that drive upwelling, biological productivity, and O2 demand within the OMZ. If equatorial Pacific winds resume their predicted weakening trend, the ocean’s largest anoxic zone will contract despite a global O2 decline.