The biogeochemical impacts of iron-rich dust to the oceans are known for Earth’s recent record but unexplored for deep time, despite recognition of large ancient dust fluxes, particularly during the late Paleozoic. We report a unique Fe relationship for Upper Pennsylvanian mudrock of eolian origin that records lowstand (glacial) conditions within a carbonate buildup of western equatorial Pangaea (western United States) well removed from other detrital inputs. Here, reactive Fe unambiguously linked to dust is enriched without a corresponding increase in total Fe. More broadly, data from thick coeval loess deposits of western equatorial Pangaea show the same marked enrichment in reactive Fe. This enrichment—atypical compared to modern marine, fluvial, glacial, loess, and soil sediments—suggests an enhancement of the reactivity of the internal Fe pool that increased the bioavailability of the Fe for marine primary production. Regardless of the mechanism behind this enhancement, our data in combination with other evidence for high dust fluxes imply delivery of extraordinarily large amounts of biogeochemically reactive Fe to glacial-stage late Paleozoic seas, and modeling of this indicates major impacts on carbon cycling and attendant climatic feedbacks.