Few studies have reported the catalytic activity of oxidized pyrite. In the paper, oxidized pyrite was first explored as a Fenton reagent to generate active species to degrade carbamazepine (CBZ) in a wide pH range (3.0–11.0). The results showed that oxidized pyrite exhibited excellent catalytic performance on the activation of H2O2 to degrade CBZ with high stability. The influences of oxidized pyrite loading, H2O2 concentration, CBZ concentration, initial pH and co-existing ions on the degradation efficiency of CBZ were studied in detail. The main active species for the degradation of CBZ were HO, O2-, e- and 1O2, which were generated from the comprehensive effects of homogeneous Fenton, heterogeneous Fenton and photo-Fenton reaction. Furthermore, a possible pathway for CBZ degradation was proposed based on the intermediates detected from UPLC-MS/MS. Finally, the potential for practical utilization of oxidized pyrite was confirmed by degrading CBZ in tap water and secondary effluent water. The obtained results provide a new idea for the environment purification using natural pyrite.