During the the terminal Cambrian Period, recurrent mass extinction and recovery events may have occurred. To test whether oceanic anoxia might have played a role in this evolutionary event, we measured U isotope compositions (d238U) in sedimentary carbonates from the The Wa’ergang section in South China to obtain the extent of global redox change during the terminal Cambrian Period.These data provide evidence for short-lived episodes of widespread marine anoxia during Stage 10, Cambrian (489 to 485 million years ago). Mass balance modeling indicates an episode of extensive oceanic anoxia, during which anoxia covered >20% of the seafloor. The results suggest that an expansion of oceanic anoxia, probably driven by intermittent sea level fall, may have contributed to the decline of the Cambrian biota.