Uranium isotopes (238U/235U) in carbonates, a proxy for global-ocean redox conditions owing to their redox sensitivity and long residence time in seawater, exhibit substantial variability in the Daxiakou section of south China from the upper-middle Permian through the mid-lower Triassic (∼9 m.y.). Middle and late Permian ocean redox conditions were similar to that of the modern ocean and were characterized by improving oxygenation in the ∼2 m.y. prior to the latest Permian mass extinction (LPME), countering earlier interpretations of sustained or gradually expanding anoxia during this interval. The LPME coincided with an abrupt negative shift of >0.5‰ in δ238U that signifies a rapid expansion of oceanic anoxia. Intensely anoxic conditions persisted for at least ∼700 k.y. (Griesbachian), lessening somewhat during the Dienerian. Th/U concentration ratios vary inversely with δ238U during the Early Triassic, with higher ratios reflecting reduced U concentrations in global seawater as a consequence of large-scale removal to anoxic facies. Modeling suggests that 70%–100% of marine U was removed to anoxic sinks during the Early Triassic, resulting in seawater U concentrations of <5% that of the modern ocean. Rapid intensification of anoxia concurrent with the LPME implies that ocean redox changes played an important role in the largest mass extinction event in Earth history.