Climate change is expected to increase the strength of ocean Oxygen Deficient Zones (ODZs), but we lack detailed understanding of the temporal or spatial variability of these ODZs. A fifty-year time series in the Eastern Tropical North Pacific (ETNP) ODZ revealed that it strengthened by 30% from 1994 to 2019. We subdivided the ODZ into a core and a deep layer based on potential density and revealed that different processes control the magnitude of fixed nitrogen loss in these two regions. We postulate that the depth of the upper ETNP ODZ water mass, the 13 ºC water, influences the organic carbon supply to the core ODZ and therefore its strength. We correlated the fixed nitrogen loss in the core ODZ with a nearby sedimentary nitrogen isotope record and found that this recent, rapid increase has only occurred a few times over the last 1200 years. Using this correlation, we derived the first confidence interval for the strength of the core ETNP ODZ, 9.2-12.5 µmol kg-1 of fixed nitrogen loss. While the current increase is comparable to only two previous events, it is still within this confidence interval. Nevertheless, climate driven intensification could lead to unprecedented changes within the next decade. The deep ODZ also strengthened from 2016-2019 by approximately 30%, even more rapidly than the core ODZ. This dramatic increase was not observed over the rest of the 50-year time series.