Free-standing masonry column is a recurrent typology of built cultural heritage. Usually raised without seismic design, columns are subject to intense rocking and overturning under strong ground motions. In this paper, a strategy to assess their seismic vulnerability using the 3-D Discrete Element Method is proposed. It includes calibrating the elastic parameters (joint stiffness parameters) using ambient vibration test data and developing fragility curves from a large set of time history analysis results. This procedure was verified for four selected water towers, a representative archaeological monument in Pompeii, Italy. Based on preliminary structural analyses, the water towers were modeled as rigid monolithic blocks. The outcomes of modal analysis were used to calibrate the input elastic parameters, starting from a range of values given by analytical calculations derived by literature. Artificial earthquakes with peak ground acceleration levels ranging from 0.167 g to 0.803 g were implemented as ground motions. Collapses and non-collapses configurations were subdivided through a threshold concerning the maximum allowable rotation of the blocks. Fragility curves were statistically developed; these revealed the overturning probabilities of the investigated structures and also enabled to conduct a parametric study of the Rayleigh damping constants.