<p>Acetone is a crucial chemical and solvent with extensive industrial applications, traditionally synthesized from propane through multi-step processes that demand high temperatures and pressures. Here, we report a selective one-step conversion of propane to acetone using a heterogeneous electro-Fenton process (h-EFP) under mild conditions. In this process, concentrated ·OH radicals are generated in an iron/carbon hybrid cathode via a two-electron oxygen reduction reaction followed by H₂O₂ conversion. Co-feeding propane and oxygen into such a cathode of an electrolyzer leads to the direct conversion of propane to acetone via isopropanol, with the acetone selectivity ranging from 50% to 80% depending on the current densities. Propane oxidation is unexpectedly accelerated at lower temperatures due to the enhanced ·OH generation. Optimal conditions are identified at 10  °C and 6.2 bar, near the propane liquefaction threshold. Furthermore, the automated separation of gaseous and liquid products at the cathode outlet enables straightforward purification of acetone to 96%. This work provides an alternative and sustainable approach to converting propane, offering a direct and efficient route for activating inert C–H bonds under mild conditions.</p>