Nanoscale zero-valent iron (nZVI) is very efficient in removing chlorinated nitroaromatic antibiotic chloramphenicol (CAP) from different waters including DI water, surface water, groundwater, and seawater. The corrosion of nZVI and product distribution after reaction in these water matrices were also investigated. Based on the identification of four main reduction products via HPLC, UPLC-MS/MS, and NMR-H spectrums, a more detailed pathway of CAP degradation by nZVI was proposed than ever reported. The two O atoms on the NO2 group were successively reduced first, and then two Cl atoms were removed via dechlorination. The process of CAP removal could be divided into two stages according to the pseudo-first-order kinetic model. A total of 97.0% of 0.30 mM CAP was rapidly removed by 1.8 mM nZVI in the first stage (6 min) with a surface-area-normalized reaction rate of 1.13 L min(-1) m(-2). Notably, after reaction with nZVI, the antibacterial activity of the CAP solution was greatly reduced. This study demonstrates that nZVI is a promising alternative to remediate CAP-contaminated water to reduce the antibiotic selection pressure of the environment.