Display omitted •TCs could be efficiently degraded by unactivated PMS.•Dimethylamino group and phenolic D ring of TCs were the main reaction sites.•Oxidation of TCs yielded O-addition, demethylation, and deamination products.•PMS oxidation could greatly eliminate the antibacterial activity of TCs.•Ca2+ and Mg2+ accelerated the oxidation of TCs by PMS due to their complexation effect. Tetracyclines (TCs) as a group of widely used antibiotics are frequent detected in aqueous environments. The transformation of tetracycline (TTC), oxytetracycline (OTC), and chlorotetracycline (CTC) as model TCs by unactivated peroxymonosulfate (PMS) during water treatment is examined in this study for the first time. Degradation of TCs by PMS showed a strong pH-dependency. The apparent second-order rate constants were in the range of 0.07–150.10 M−1s−1 (pH 5.0–10.0). Products analysis showed that PMS primarily reacted with TCs at their unprotonated dimethylamino group and deprotonated phenolic-diketone group, leading to the formation of O-addition, demethylation, and deamination products. Water hardness Ca2+ and Mg2+ appreciably accelerated the degradation of TCs by PMS due to their strong complexation with TCs, while chloride, bicarbonate, and natural organic matter at environmental relevant concentrations had negligible impacts. Transformation products of TCs showed negligible antibacterial activity comparing with the parent TCs by using Escherichia coli. as test bacteria. The degradation of TCs by PMS in real waters was appreciably faster than that in pure water, and the presence of background Ca2+ and Mg2+ in real waters accounted for this enhancing effect. Unactivated PMS exhibits great potential for the removal of TCs and their antibacterial activity from contaminated waters.