Herein, the novel application of FeS2/C nanocomposite as a highly active, stable, and recyclable catalyst for heterogeneous electro-Fenton (EF) treatment of organic water pollutants is discussed. The simultaneous carbonization and sulfidation of an iron-based metal-organic framework (MOF) yielded well-dispersed pyrite FeS2 nanoparticles of ∼100 nm diameter linked to porous carbon. XPS analysis revealed the presence of doping N atoms. EF treatment with an IrO2/air-diffusion cell ensured the complete removal of the antidepressant fluoxetine spiked into urban wastewater at near-neutral pH after 60 min at 50 mA with 0.4 g L-1 catalyst as optimum dose. The clear enhancement of catalytic activity and stability of the material as compared to natural pyrite was evidenced, as deduced from its characterization before and after use. The final solutions contained <1.5 mg L-1 dissolved iron and became progressively acidified. Fluorescence excitation-emission spectroscopy with parallel factor analysis demonstrated the large mineralization of all wastewater components at 6 h, which was accompanied by a substantial decrease of toxicity. A mechanism with •OH as the dominant oxidant was proposed: FeS2 core-shell nanoparticles served as Fe2+ shuttles for homogeneous Fenton's reaction and provided active sites for the heterogeneous Fenton process, whereas nanoporous carbon allowed minimizing the mass transport limitations.