Historic observations of dissolved oxygen (O-2) in the ocean are analyzed to quantify multidecadal trends and variability from 1958 to 2015. Additional quality control is applied, and the resultant oxygen anomaly field is used to quantify upper ocean O-2 trends at global and hemispheric scales. A widespread negative O-2 trend is beginning to emerge from the envelope of interannual variability. Ocean reanalysis data are used to evaluate relationships with changes in ocean heat content (OHC) and oxygen solubility (O-2,O-sat). Global O-2 decline is evident after the 1980s, accompanied by an increase in global OHC. The global upper ocean O-2 inventory (0-1000m) changed at the rate of -243124TmolO(2) per decade. Further, the O-2 inventory is negatively correlated with the OHC (r=-0.86; 0-1000m) and the regression coefficient of O-2 to OHC is approximately -8.20.66nmolO(2)J(-1), on the same order of magnitude as the simulated O-2-heat relationship typically found in ocean climate models. Variability and trends in the observed upper ocean O-2 concentration are dominated by the apparent oxygen utilization component with relatively small contributions from O-2,O-sat. This indicates that changing ocean circulation, mixing, and/or biochemical processes, rather than the direct thermally induced solubility effects, are the primary drivers for the observed O-2 changes. The spatial patterns of the multidecadal trend include regions of enhanced ocean deoxygenation including the subpolar North Pacific, eastern boundary upwelling systems, and tropical oxygen minimum zones. Further studies are warranted to understand and attribute the global O-2 trends and their regional expressions. Plain Language Summary This new paper describes the analysis of the dissolved oxygen in the global ocean using the most recent version of the World Ocean Database for the period of 1955 to 2015. After careful examination of the data, we found that a statistically significant, widespread O-2 decline is emerging beyond the envelope of natural fluctuations. Our study also reveals a tight relationship between O-2 inventories and the ocean heat content. The spatial pattern and magnitude of this relationship are consistent with expectations derived from mechanistic ocean climate models forced under climate warming scenarios. Taken together, the trends we document here are suggestive of the effects of the ocean warming beginning to supersede natural variability and emerge as a recognizable signal. This merits additional scrutiny over the coming years.