As a natural organic carbon skeleton, humic acid (HA) was loaded with nanoscale zero-valent iron (nZVI) Particles to remove chloramphenicol (CAP) from aqueous solution. The pore morphology and structure, the type, the distribution and valence state of element, and the class of functional groups on the surface of the material were shown by SEM/EDS, XPS, BET and FTIR. When the load ratio of nZVI on HA was 1:30, the iron content in the material was minimized, the specific gravity of the economic material-HA was increased, and the removal efficiency of CAP was 80.0% or higher. In addition, the mass ratio of nZVI on HA, the dosage of nZVI/HA-30, the initial pH and CAP concentration of the solution, these four general factors, played an important role in the efficiency and equilibrium time of the CAP removal. The removal efficiency of CAP by nZVI/HA-30 was 84.2% when the dosage was 1.0 g (100 mL)−1, the initial concentration of CAP was 30 mg L−1 and the pH was 3. The reaction pathway and removal mechanism of ZVI/HA-30 were studied by the concentration of total and ferrous iron ions in the solution, UV–Vis and MS. The CAP was continuously denitrified and dechlorinated, decomposed into easily degradable substances by nZVI particles supported on HA, which was consistent with the first-order kinetic model within 5 min. This newly synthesized material was economical and efficient, easy to store, effectively prevented agglomeration and passivation of nZVI, and had a good application prospect for removing contaminants from water.