The electro-Fenton (EF) and photoelectro-Fenton (PEF) degradation of solutions of the beta-blocker propranolol hydrochloride with 0.5 mmol dm−3 Fe2+ at pH 3.0 has been studied using a single cell with a boron-doped diamond (BDD) anode and an air diffusion cathode (ADE) for H2O2 electrogeneration and a combined cell containing the above BDD/ADE pair coupled in parallel to a Pt/carbon felt (CF) cell. This naphthalene derivative can be mineralized by both methods with a BDD anode. Almost overall mineralization is attained for the PEF treatments, more rapidly with the combined system due to the generation of higher amounts of hydroxyl radical from Fenton's reaction by the continuous Fe2+ regeneration at the CF cathode, accelerating the oxidation of organics to Fe(III)–carboxylate complexes that are more quickly photolyzed by UVA light. The homologous EF processes are less potent giving partial mineralization. The effect of current density, pH and Fe2+ and drug concentrations on the oxidation power of PEF process in combined cell is examined. Propranolol decay follows a pseudo first-order reaction in most cases. Aromatic intermediates such as 1-naphthol and phthalic acid and generated carboxylic acids such as maleic, formic, oxalic and oxamic are detected and quantified by high-performance liquid chromatography. The chloride ions present in the starting solution are slowly oxidized at the BDD anode. In PEF treatments, all initial N of propranolol is completely transformed into inorganic ions, with predominance of NH4+ over NO3− ion.