Tidal wetlands, crucial carbon sinks with high productivity, face threats from sea-level rise due to climate change. It is unclear how sea level rise-driven salinization will impact the processes controlling the stability of organic matter in these wetlands. Hydroxyl radicals (·OH) are a short-lived yet powerful nonselective oxidant of organic matter that can be produced by non-photochemical (“dark”) Fenton reactions at subsurface oxic-anoxic interfaces, and they may play a role in degradation of recalcitrant organic matter in wetland sediments. This study aimed to explore the connections between coupled biogeochemical cycling of iron (Fe) and sulfur (S) in wetland sediments and the generation of hydroxyl radicals (·OH), and how these interactions are affected by seawater-derived sulfate (SO42-) and chloride (Cl-) ions which are known to impact the speciation and reactivity of Fe. Field measurements from brackish and freshwater tidal wetlands along the Hudson River Estuary showed higher ·OH concentrations at the brackish site, attributed to greater sediment concentrations of mackinawite (FeS) due to higher concentrations of seawater-derived S. Laboratory experiments with oxygenation of FeS synthesized with a range of Fe:S ratios, and reduction and oxidation of freshwater sediment amended with different concentrations of SO42-, confirm that FeS promotes ·OH formation, and also constrains the effect of Cl- quenching of ·OH formation. This evidence underscores the significance of increasing salinity on Fe-S cycling in tidal wetland sediments with implications for ·OH production and potential impacts on organic matter mineralization.