Estuarine sediments are pivotal zones for iron (Fe) cycling, mediated by microbial communities and coupled to carbon, nitrogen, sulfur and phosphorus transformations. However, the microbial iron metabolic processes in estuarine sediments remain poorly characterized, particularly under hypoxia. This study compared metagenomes from the Oujiang River Estuary, an oxic estuary, and the Yangtze River Estuary, a seasonally hypoxic estuary, complemented by sediment core incubations to assess geochemical responses to deoxygenation. The taxonomic affiliations of iron metabolism-related genes in the oxic estuary were homogeneous with depth, dominated by Proteobacteria and Thermodesulfobacteriota. In contrast, the hypoxic estuary exhibited strong stratification, with the surface enriched in Proteobacteria and deeper horizons dominated by Chloroflexota and Candidatus Bathyarchaeota. The surface sediments of the hypoxic estuary at 0–8 centimeters below the seafloor showed a hotspot with co-enrichment of dissimilatory iron reduction (e.g., mtrABC) and iron oxidation genes (e.g., mtoA) relative to both deeper layers in the same estuary and the oxic estuary, consistent with elevated genetic potential for Fe redox turnover. This hotspot also harbored high-affinity Fe acquisition systems (siderophores, inorganic Fe transporters, and heme uptake), suggesting the potential for microbial competition for iron. Co-occurrence networks connecting Fe metabolism with carbon, nitrogen, sulfur and phosphorus cycling were more complex in the hypoxic estuary than in the oxic estuary, revealing strong associations between Fe acquisition/ redox cycling and organic matter turnover. A 16-day incubation of sediment cores from the oxic estuary showed that short-term deoxygenation enhanced dissolved Fe, phosphate, and ammonium release. Overall, our results suggest that bottom-water hypoxia is associated with major shifts in microbial iron metabolism potential, with implications for iron-organic matter interactions and nutrient regeneration under coastal deoxygenation.