Since the discovery of the potential hazards of ciprofloxacin (CIP) to the ecosystem and human health, there has been an urgent need to develop effective technologies to solve the severe issue. In this work, the nanozero-valent iron graphitized carbon matrix (xFe@CS-Tm) were prepared via a hydrothermal method to activate peroxydisulfate (PDS) for degradation of CIP. Specifically, 0.5Fe@CS-T7 exhibited the excellent catalytic performance for PDS activation to degrade CIP. Moreover, the catalyst exhibited vigorous interference resistance at various pH values, in the presence of various inorganic anions and under humic acid conditions. The characterization results demonstrated that Fe was successfully embedded on the carbon matrix and became the active sites to promote ROS production. It is demonstrated that O2•− was the main active species rather than •OH and SO4•−, based on quench trapping, EPR experiments and steady state concentrations calculations. The possible pathways of CIP degradation were proposed using LC–MS results and density functional theory. The outcomes of the toxicity estimation software tool found that the toxicity of CIP was reduced. This study not only investigated a novel methodology for the degradation of antibiotic wastewater but also provides a feasible pathway for carbon-neutral wastewater treatment.