Ocean oxygen content is decreasing with global change. A major challenge for modelling future declines in oxygen concentration is our lack of knowledge of the natural variability associated with marine oxygen inventory on interannual and multidecadal timescales. Here, we present 10 annually resolved 200 year-long records of denitrification, a marker of deoxygenation, from a varved sedimentary archive in the North Pacific oxygen minimum zone covering key periods over the last glacial–interglacial cycle. Spectral analyses on these records reveal strong signals at periodicities typical of today’s Atlantic multidecadal oscillation. Modern subsurface circulation reanalyses regressed on the positive Atlantic and Pacific Climatic Oscillation indices further confirm that North Atlantic temperature patterns are the main control on the subsurface zonal circulation and therefore the most likely dominant driver of oxygen variability in the tropical Pacific. With currently increasing temperatures in the Northern Hemisphere high latitudes and North Atlantic, we suggest deoxygenation will intensify in the region.