Calcium　peroxide　(CaO2)　has　been　increasingly　used　as　a　disinfectant.　However,　the　effects　of　ferrous　ions　on　CaO2　activation　and　the　corresponding　removal　of　typical　fecal　contamination　indicators　(e.g.　Escherichia　coli)　and　the　associated　ARGs　in　the　aquaculture　pond　remain　unknown.　To　address　this　question,　the　application　of　Fe2　+/CaO2　in　degrading　the　typical　aquaculture　antibiotic　tetracycline　(TC),　inactivating　the　fecal　contamination　indicator　E.　coli　K12　and　removing　its　intracellular　ARGs　(iARGs)　and　extracellular　ARGs　(eARGs)　was　investigated.　The　results　demonstrated　that　TC　and　E.　coli　K12　could　be　completely　removed　at　a　Fe2+　to　CaO2　molar　ratio　of　2.　Electron　paramagnetic　resonance　(EPR)　and　scavenging　tests　indicated　the　presence　of　•OH,　•O₂⁻　and　1O2,　with　•OH　and　1O2　likely　being　the　dominant　active　species　responsible　for　this　process.　The　first-order　inactivation　rate　constant　of　E.　coli　K12　in　Fe2+/CaO2　treatment　was　significantly　higher　than　in　CaO2　treatment.　Furthermore,　copper　ions　can　promote　the　inactivation　of　pathogens,　while　humic　acid　and　certain　anions　(e.g.　Cl-)　negatively　affect　the　inactivation　of　E.　coli　K12　by　Fe2+/CaO2.　We　further　found　that　Fe2+/CaO2　could　efficiently　remove　iARGs　and　reduce　the　accumulation　of　eARGs,　outperforming　common　disinfection　technologies　in　the　removal　of　TC,　E.　coli　K12,　as　well　as　iARGs　and　eARGs　in　real　aquaculture　surface　water.　These　results　highlight　that　Fe2+/CaO2　with　lower　treatment　costs　excels　in　the　simultaneous　control　of　antibiotics,　fecal　indicators,　and　ARGs　in　aquaculture　ponds　in　neutral　pH　aquaculture　water,　ensuring　safety　and　efficiency.　©　2025　Elsevier　Ltd