The rates of marine deoxygenation leading to Cretaceous Oceanic Anoxic Events are poorly recognized and constrained. If increases in primary productivity are the primary driver of these episodes, progressive oxygen loss from global waters should predate enhanced carbon burial in underlying sediments - the diagnostic Oceanic Anoxic Event relic. Thallium isotope analysis of organic-rich black shales from Demerara Rise across Oceanic Anoxic Event 2 reveals evidence of expanded sediment-water interface deoxygenation ~43 ± 11 thousand years before the globally recognized carbon cycle perturbation. This evidence for rapid oxygen loss leading to an extreme ancient climatic event has timely implications for the modern ocean, which is already experiencing large-scale deoxygenation.