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 δ¹³C_carb) and global climate conditions. δ²³⁸U varied in a coordinated, mostly positive relationship with δ¹³C_carb, 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 δ¹³C_carb) 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.