A novel graphitic carbon nitride containing non-intrinsic oxygen vacancies (Vo-CN) is interfacial coupling with zinc indium sulfide (ZIS) to form Z-scheme heterojunction (VCZ) for efficient tetracycline (TC) degradation. The TC removal rate by VCZ-1 (mass ratio of Vo-CN: ZIS is 1:20, 0.2 g/L) achieves 99.86 %. VCZ-1 reveals outstanding reusability and stability with an unchanged TC degradation rate after undergoing five cycles. VCZ-1 achieves high-efficiency TC degradation in various water matrices. The experimental and DFT calculations indicate that the built-in electric field drives charges on Vo-CN transfer to ZIS, forming a Z-scheme VCZ-1 heterojunction. The strong electronic coupling effect between Vo-CN and ZIS facilitates charge exchange at the heterojunction interface. Non-intrinsic oxygen vacancies in VCZ, as binding sites for electrons and holes, effectively lower the energy barrier for singlet excitons converting to triplet excitons. The triplet excitons are induced to transfer energies to dissolved oxygen and expedite 1O2 production. 1O2 synergizes with •O2– and •OH to attack O-containing groups and hexatomic rings in TC, inducing demethylation, hydroxylation, dihydroxylation, and ring-opening reactions. Three possible degradation pathways are inferred by UPLC/MS/MS and Fukui index of TC. The ecotoxicity evaluation of intermediate products highlights the benefits of VCZ-1 photocatalytic oxidation in ensuring environmental safety. This work proposes a novel idea for constructing efficient Z-scheme photocatalysts for environmental remediation.