The oxygen minimum zones (OMZ) are especially sensitive to ocean deoxygenation due to the nonlinear dependence of their size on the oxygen inventory. Significant decadal variability has been observed in the extent and intensity of the tropical Pacific OMZ. Here we diagnose the physical and biogeochemical mechanisms behind the interannual and decadal variability of oxygen in the tropical Pacific thermocline using a three-dimensional ocean biogeochemistry model that reproduces the expansion of the tropical Pacific OMZ since the 1980s. On interannual time scales, heat content and respiration rates are strongly influenced by El Niño-Southern Oscillation cycles and the associated changes in upwelling. The resulting changes in solubility and apparent oxygen utilization tend to compensate one another, thus damping the magnitude of oxygen variability. Regional oxygen budget reveals the subtle balance between the lateral and vertical ocean circulation in controlling the physical oxygen supply to the eastern tropical Pacific. Spectral analysis shows that the tropical Pacific oxygen has a stronger variance in decadal time scales than its physical and biological drivers. Our results suggest that the physical oxygen supply and biological oxygen loss are integrated through the finite memory of thermocline waters to produce the multidecadal variability of OMZ.