Solutions with 0.65 mM of the antituberculosis drug isoniazid (INH) in 0.050 M NaSO at pH 3.0 were treated by electro-Fenton (EF) and UVA photoelectro-Fenton (PEF) processes using a cell with a BDD anode and a carbon-PTFE air-diffusion cathode. The influence of current density on degradation, mineralization rate, and current efficiency has been thoroughly evaluated in EF. The effect of the metallic catalyst (Fe or Fe) and the formation of products like short-chain linear aliphatic carboxylic acids were assessed in PEF. Two consecutive pseudo-first-order kinetic regions were found using Fe as catalyst. In the first region, at short time, the drug was rapidly oxidized by OH, whereas in the second region, at longer time, a resulting Fe(III)-INH complex was much more slowly removed by oxidants. INH disappeared completely at 300 min by EF, attaining 88 and 94% mineralization at 66.6 and 100 mA cm, respectively. Isonicotinamide and its hydroxylated derivative were identified as aromatic products of INH by GC-MS and oxalic, oxamic, and formic acids were quantified by ion-exclusion HPLC. The PEF treatment of a real wastewater polluted with the drug led to slower INH and TOC abatements because of the parallel destruction of its natural organic matter content.