In recent years, the blast resistance of hydraulic structures under explosion loads has attracted more and more attention. The damage calculation method of prestressed aqueducts subjected to blasting load is still a complicated problem. For this purpose, the theory of computation of the water pressure blasting is introduced and the formula for calculating the charge weight of the water pressure blasting is presented. The accuracy of the Coupled Eulerian-Lagrangian (CEL) algorithm of the underwater explosion model is verified by the previous experiment. Then, a fully coupled three-dimensional numerical model of a prestressed aqueduct is established to acquire the dynamic performances and failure mechanisms of the prestressed aqueduct subjected to water pressure blasting. The influence of the prestress and pull rod on nonlinear dynamic performances and failure modes of a prestressed aqueduct subjected to water pressure blasting are discussed. Finally, based on the wave and material mechanics, a method of calculation for the prestressed aqueduct subjected to water pressure blasting is presented. The accuracy of the suggested method is validated by the damage mode of the prestressed aqueduct subjected to water pressure blasting under various TNT weights. The analysis results show that the proposed method can satisfy the relationship between the damage characteristics of the prestressed aqueduct to water pressure blasting and various TNT weights. 1.5 kg TNT is insufficient to completely shatter the prestressed aqueduct, while 3.5 kg TNT can cause a perfect crushing effect. 7.5 kg TNT will result in excessive fragmentation of the prestressed aqueduct and inefficient utilization of the explosive energy. The proposed damage calculation method can provide significant support for explosion analysis of the prestressed thin-walled aqueduct structure.