Display omitted •Fe0 is an efficient and long-lasting activator of PMS for the degradation of tetracycline.•The main radical species play a dominant role in the degradation of tetracycline.•The intermediates of tetracycline were detected and the possible degradation pathway was elaborated.•The toxicity of tetracycline in reaction solution finally reduced after Fe0/PMS process. In this paper, the degradation of tetracycline (TC) by peroxymonosulfate (PMS) activated with zero-valent iron (Fe0) was systematically studied through batches of experiments. First, effects of the key parameters (i.e., Fe0 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 Fe0/PMS process and the synergistic effect between Fe0 and PMS. Compared with Fe2+ (the relatively common PMS activator), Fe0 was an efficient and long-lasting activator which consume less PMS and produce less dissolved iron ions. Then, the characteristics of reacted Fe0 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 Fe0 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.