The generation of reactive oxygen species (ROS) via the Fenton reaction has received significant attention for widespread applications. This reaction can be triggered by zero-valent metal nanoparticles by converting externally added H2O2 into hydroxyl radicals (˙OH) in acidic media. To avoid the addition of external additives or energy supply, developing self-sustained catalytic systems enabling onsite production of H2O2 at a neutral pH is crucial. Here, we present novel galvanic nanocells (GNCs) based on metallic Fe/Au bilayers on arrays of nanoporous silica nanostructures for the generation of self-sustained Fenton reactions. These GNCs exploit the large electrochemical potential difference between the Fe and Au layers to enable direct H2O2 production and efficient release of Fe2+ in water at neutral pH, thereby triggering the Fenton reaction. Additionally, the GNCs promote Fe2+/Fe3+ circulation and minimize side reactions that passivate the iron surface to enhance their reactivity. The capability to directly trigger the Fenton reaction in water at pH 7 is demonstrated by the fast degradation and mineralization of organic pollutants, by using tiny amounts of catalyst. The self-generated H2O2 and its transformation into ˙OH in a neutral environment provide a promising route not only in environmental remediation but also to produce therapeutic ROS and address the limitations of Fenton catalytic nanostructures.