Iron immobilized on supports such as silica, alumina, titanium oxide, and zeolite can activate hydrogen peroxide (H₂O₂) into strong oxidants. However, the role of the support and the nature of the oxidants produced in this process remain elusive. This study investigated the activation of H₂O₂ by a TiO₂-supported catalyst (FeTi-ox). Characterizing the catalyst surface in situ using X-ray absorption spectroscopy (XAS), together with X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR), revealed that the interaction between H₂O₂ and the TiO₂ phase played a key role in the H₂O₂ activation. This interaction generated a stable peroxo–titania ≡Fe(III)–Ti–OOH complex, which reacted further with H2O to produce a surface oxidant, likely ≡Fe[IV] ═ O²⁺. The oxidant effectively degraded acetaminophen, even in the presence of chloride, bicarbonate, and organic matter. Unexpectedly, contaminant oxidation continued after the H2O2 in the solution was depleted, owing to the decomposition of ≡Fe(III)–Ti–OOH by water. In addition, the FeTi-ox catalyst effectively degraded acetaminophen over five testing cycles. Overall, new insights gained in this study may provide a basis for designing more effective catalysts for H₂O₂ activation.