The cause of the Frasnian-Famennian boundary (FFB) biotic crisis, one of the “Big Five” Phanerozoic mass extinctions, remains poorly understood. Here, we generated a high-resolution uranium-isotope profile (δ238U) for a marine carbonate section at Baisha, South China, in order to document secular variation in mean global-ocean redox conditions and to compare its relationship to coeval changes in organic carbon burial fluxes (as proxied by δ13Ccarb) and global climate conditions. δ238U varied in a coordinated, mostly positive relationship with δ13Ccarb, indicating that expanded (reduced) oceanic anoxia was linked to lower (higher) productivity. This pattern is inconsistent with productivity control of redox conditions and suggests instead that both proxies responded to a common climatic forcing. We infer that climatic cooling (and glaciation during the Upper Kellwasser Horizon [UKH] event) led to better-ventilated oceanic conditions (higher δ238U) and greater productivity (higher δ13Ccarb) owing to invigoration of global-ocean overturning circulation and enhanced upwelling. Because the UKH event coincided with the FFB mass extinction, cooling rather than oceanic anoxia may have been the main killing mechanism.