Nanoscale catalysts that can enable Fenton-like chemistry and produce reactive radicals from hydrogen peroxide activation have been extensively studied in order to overcome the limitations of homogeneous Fenton processes. Despite several advantageous features, limitation in mass transfer of short-lived radical species is an inherent drawback of the heterogeneous system. Here, we present a mechanistic foundation for the way spatial confinement of Fenton chemistry at the nanoscale can significantly enhance the kinetics of radical-mediated oxidation reactions—pollutant degradation in particular. We synthesized a series of Fe₃O₄-functionalized nanoreactors with precise pore dimensions, based on an anodized aluminum oxide template, to enable quantitative analysis of nanoconfinement effects. Combined with computational simulation of spatial distribution of radicals, we found that hydroxyl radical concentration was strongly dependent on the distance from the surface of Fenton catalysts. This distance dependency significantly influences the gross reaction kinetics and accounts for the observed nanoconfinement effects. We further found that a length scale below 25 nm is critical to avoid the limitation of short-lived species diffusion and achieve kinetics that are orders of magnitude faster than those obtained in a batch suspension of heterogeneous catalysts. These findings suggest a new strategy to develop an innovative heterogeneous catalytic system with the most effective use of hydroxyl radicals in oxidation treatment scenarios.