During CO2 geological sequestration, interfacial micro-annuli generated by sealing failure of the wellbore cement sheath are recognized as the primary pathways for CO2 leakage. Current evaluation approaches for cement sheath sealing performance are mostly confined to scaled?down models or static characterizations, which fail to reproduce the complex gas?liquid environments and transient seepage behavior within full?scale wellbore micro?annuli. To address this gap, the flow resistance and sealing performance of four cement systems with distinct formulations were systematically evaluated under both gas and liquid conditions, integrating full?scale physical simulation experiments with a developed three?dimensional finite element equivalent seepage model. Quantitative analysis based on interfacial anti?channeling and equivalent permeability reveals that the modified system, containing high?dosage silica fume and toughening agents, exhibits markedly enhanced barrier capacity and significantly increases both gas and liquid breakthrough pressure thresholds relative to standard Class G cement. In addition, the transient pressure field evolution and flow rate development were visually replicated by the finite element seepage model, shedding light on the interfacial leakage mechanisms governed by differences in fluid physical properties. The simulated dynamic flow evolution shows strong consistency with the fluid retardation phenomena observed in physical experiments—characterized by delayed liquid advancement and higher required driving pressures—thus confirming the physical fidelity and reliability of the numerical model. This work offers a robust theoretical basis and technical guidance for optimizing anti?channeling cement formulations in CCUS injection wells and ensuring the integrity of long?term geological storage.