The early evolutionary and much of the extinction history of marine animals, is thought to be driven by changes in dissolved oxygen concentrations ([O2]) in the ocean1–3. In turn, [O2] is widely assumed to be dominated by the geological history of atmospheric oxygen (pO2)4,5. Here, in contrast, we show via a series of Earth system model experiments how continental rearrangement during the Phanerozoic drives profound variations in ocean oxygenation and induces a fundamental decoupling in time between upper-ocean and benthic [O2]. We further identify the presence of (paleogeographical) state-dependent modes of circulation instability (oscillations), which allows for pO2 to already be close to modern by the beginning of the Phanerozoic despite the deep ocean remaining anoxic. The occurrence of extreme volatility in ocean oxygenation also provides a causal mechanism explaining elevated rates of metazoan radiation and extinction during the early Paleozoic6. The absence in our modelling of any simple correlation between global climate and ocean ventilation together with the occurrence of profound variations in ocean oxygenation independent of atmospheric pO2, presents both a challenge to the interpretation of marine redox proxies, but also points to a hitherto unrecognized role for continental configuration in the evolution of the biosphere.