In this paper, a novel numerical model for characterizing the seepage and dissolution coupling effect on the durability of anti-seepage walls of earth-rock dams is proposed. The model considers the influence of hydraulic gradient-driven seepage on the non-equilibrium decomposition of the calcium dissolution in concrete, as well as the effects of seepage dissolution on pore structure, permeability, and diffusivity. The reasonableness of the model is validated by experimental and literature data, which is then applied to analyze the deterioration and failure processes of a concrete cutoff wall of an earth-rock dam in Zhejiang Province, China. On this basis, the seepage dissolution durability control indices of anti-seepage walls are identified. The findings demonstrate that the suggested method accurately explains the calcium leaching process in concrete. Under the seepage and dissolution coupling effect, calcium in the wall continuously decomposes and precipitates, leading to varying degrees of increases in structural performance parameters, which weaken the seepage control performance of the walls and consequently result in an increase in seepage discharge and hydraulic gradient. By proposing the critical hydraulic gradient as a criterion, the service life of the wall is projected to be 42.8 years. Additionally, the upstream hydraulic head, the initial permeability coefficient, and the calcium hydroxide (CH) content are three crucial indices affecting the durability of walls, and these indices should be reasonably controlled during the engineering design, construction, and operational phases.