Microwave-induced catalytic degradation (MICD) has been considered as one of the most prospective approaches to remove organic contaminants from water. High-performance catalysts, ideally offering efficient degradation ability, are essential to this process. This work reports the fabrication of manganese oxide on carbon nanotubes (MnO/CNTs) as an efficient catalyst under microwave irradiation (MI) to remove tetracycline (TC) from aqueous solution. The hybrid MnO/CNTs structure shows excellent performance in TC degradation. Combining experimental characterization and theoretical calculations, synergistic mechanisms are revealed: (i) Strong MnO/CNTs interaction stabilizes Mn(II) through interfacial bonding; (ii) high-spin states associated with low coordinated Mn(II) play a major role in MICD; and (iii) superoxide radicals (•O2−) and hydroxyl radicals (•OH) induced by microwave input are identified as the major active species.