Historic observations of dissolved oxygen (O2) 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 O2 trends at global and hemispheric scales. A widespread negative O2 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 (O2,sat). Global O2 decline is evident after the 1980s, accompanied by an increase in global OHC. The global upper ocean O2 inventory (0-1000 m) changed at the rate of -243 ± 124 T mol O2 per decade. Further, the O2 inventory is negatively correlated with the OHC (r = -0.86; 0-1000 m) and the regression coefficient of O2 to OHC is approximately -8.2 ± 0.66 nmol O2 J-1, on the same order of magnitude as the simulated O2-heat relationship typically found in ocean climate models. Variability and trends in the observed upper ocean O2 concentration are dominated by the apparent oxygen utilization component with relatively small contributions from O2,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 O2 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 O2 trends and their regional expressions.