In this paper, the degradation of tetracycline (TC) by peroxymonosulfate (PMS) activated with zero-valent iron (Fe-0) was systematically studied through batches of experiments. First, effects of the key parameters (i.e., Fe-0 dosage, PMS dosage, initial pH and co-existing ions) on TC degradation were investigated. Under the optimal conditions, high TC removal efficiency (88.5%) was achieved after 5 min treatment. Also, four control experiments were conducted to demonstrate the excellent performance of Fe-0/PMS process and the synergistic effect between Fe-0 and PMS. Compared with Fe2+ (the relatively common PMS activator), Fe-0 was an efficient and long-lasting activator which consume less PMS and produce less dissolved iron ions. Then, the characteristics of reacted Fe-0 particles were analyzed by SEM-EDS, XRD and XPS. The results shows that a few iron corrosion products generated and some of them deposited on the surface of reacted Fe-0 particles. The generated iron corrosion products could promote PMS activation or adsorb TC directly. Next, the possible degradation pathway of TC was elaborated according to the intermediates detected by LC-QTOF-MS/MS and the toxicity in solution during reaction was evaluated. Finally, the common free radicals were monitored and the reaction mechanism was proposed.