Uranium isotopes (238U/235U) have been used widely over the last decade as a global proxy for marine redox conditions. The largest isotopic fractionations in the system occur during U reduction, removal and burial. Applying this basic framework, global U isotope mass balance models have been used to predict the extent of ocean floor anoxia during key intervals throughout Earth’s history. However, there are currently minimal constraints on the isotopic fractionation that occurs during reduction and burial in anoxic and iron-rich (ferruginous) aquatic systems, despite the consensus that ferruginous conditions are thought to have been widespread through the majority of our planet’s history. Here we provide the first exploration of 238U values in natural ferruginous settings. We measured 238U in sediments from two modern ferruginous lakes (Brownie Lake and Lake Pavin), the water column of Brownie Lake, and sedimentary rocks from the Silurian-Devonian boundary that were deposited under ferruginous conditions. Additionally, we provide new 238U data from core top sediments from anoxic but non-sulfidic settings in the Peru Margin oxygen minimum zone. We find that 238U values from sediments deposited in all of these localities are highly variable, but on average are indistinguishable from adjacent oxic sediments. This forces a reevaluation of the global U isotope mass balance and how U isotope values are used to reconstruct the evolution of the marine redox landscape.