A methodology aiming to predict the vulnerability of masonry structures under seismic action is presented herein. Masonry structures, among which many are cultural heritage assets, present high vulnerability under earthquake. Reliable simulations of their response to seismic stresses are exceedingly difficult because of the complexity of the structural system and the anisotropic and brittle behavior of the masonry materials. Furthermore, the majority of the parameters involved in the problem such as the masonry material mechanical characteristics and earthquake loading characteristics have a stochastic-probabilistic nature. Within this framework, a detailed analytical methodological approach for assessing the seismic vulnerability of masonry historical and monumental structures is presented, taking into account the probabilistic nature of the input parameters by means of analytically determining fragility curves. The emerged methodology is presented in detail through application on theoretical and built cultural heritage real masonry structures.