An approach to analyze the seismic reliability of water distribution networks by combining a hydraulic analysis with a first-order reliability method (FORM), is proposed in this paper. The hydraulic analysis method for normal conditions is modified to accommodate the special conditions necessary to perform a seismic hydraulic analysis. In order to calculate the leakage area and leaking flow of the pipelines in the hydraulic analysis method, a new leakage model established from the seismic response analysis of buried pipelines is presented. To validate the proposed approach, a network with 17 nodes and 24 pipelines is investigated in detail. The approach is also applied to an actual project consisting of 463 nodes and 767 pipelines. The results show that the proposed approach achieves satisfactory results in analyzing the seismic reliability of large-scale water distribution networks.