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The Late Devonian extinction ranks as one of the ‘big five’ Phanerozoic extinctions affecting up to 80% of marine species and occurred during five distinct pulses spanning /or widespread marine anoxia. We test the marine anoxia hypothesis by analyzing uranium isotopes (δ238U) across a ~7 My interval of well-dated Upper Devonian marine carbonates from the Devil’s Gate Limestone in Nevada, USA. The measured δ238U curve shows no co-variation with local anoxic facies, water-depth dependent facies changes, redox-sensitive metals, TOC, or diagnostic elemental ratios indicating the δ238U curve was not controlled by local depositional or diagenetic processes and represents global seawater redox conditions. Two negative δ238U shifts (indicating more reducing seawater) are observed with durations of ~3.8 My (late Frasnian) and ~1.1 My (early Famennian), respectively. Steady-state modeling of the observed -0.2 to -0.3‰ shifts in δ238U points to a ~5-15% increase in the total area of anoxic seafloor during these excursions. The late Frasnian negative shift is broadly coincident with the first extinction pulse (late rhenana Zone or lower Kellwasser event), whereas the early Famennian negative shift (lower-middle triangularis zones) does not coincide with the most intense Frasnian-Famennian boundary (F-F) extinction pulses (upper Kellwasser event). Compilations of local sediment redox conditions from Upper Devonian marine deposits with conodont zone-level age control indicates that the extinction pulses were coincident with widespread anoxic deposits accumulating in subtropical epeiric sea and some open-ocean settings supporting previous interpretations that widespread marine anoxia had an important influence on the Late Devonian extinction. The temporal relationships between global ocean redox trends represented by the δ238U curve and the newly compiled subtropical marine redox sediment trends indicates Late Devonian global oceans and epeiric seas were in relatively good redox communication for the majority of the study interval except for a brief interval (ky) spanning the F-F boundary.