During the Mesozoic greenhouse world, the oceans underwent several oceanic anoxic events (OAEs) characterized by intervals during which organic-rich black shales were deposited, indicating strong oxygen depletion in the marine realm. The Cenomanian-Turonian OAE2 (ca. 93 Ma) represents one of the most prominent events of the Cretaceous, with significant perturbations of the global carbon cycle. Although OAE2 likely reached a global scale, the spatial extent of seawater anoxia during this OAE is poorly constrained. Here we demonstrate that variations in the 238U/235U isotope ratio (δ238U), a newly developed paleoredox proxy, can be used to quantify the extent of marine anoxia. For black shales from the mid-Cretaceous OAE2 we find a systematic shift toward lighter δ238U and lower U concentrations as compared to modern equivalent organic-rich sediments from the Black Sea. This shift translates to a global increase of oceanic anoxia during OAE2 by at least a factor of three as compared to the present day or to periods before and after OAE2. The constant offset in U concentrations and isotope compositions of black shales throughout OAE2 compared to modern Black Sea sediments indicates an enhancement of oceanic anoxic conditions already prior to the onset of OAE2.