Monumental buildings are by definition unique buildings that cannot be reduced to any standard structural scheme: this makes it difficult to evaluate their seismic reliability, because—in addition to the many uncertainties that are common to all existing (and in particular “old”) buildings—no statistics on the behaviour of similar buildings can be available. To overcome this problem, the macroelement approach has been proposed a few years ago and since then repeatedly used to analyse and compare the seismic response of monumental buildings: the structural organism is considered as the assemblage of few components (e.g. the whole façade of a church) whose behaviour is typical of the behaviour of analogous macroelements in other buildings, and whose possible collapse mechanisms can be identified. In these studies, quasi-static loads have been used, as indeed common in many analyses of the seismic behaviour of masonry structures. This paper accepts these simplifying assumptions, and shows how—assuming appropriate probabilistic properties of the relevant quantities and a “logical diagram” describing the relation between collapse of macroelements and whole building—the probability of collapse and damage of each macroelement and of the whole building under given horizontal loads can be assessed. The procedure is formulated in detail with special reference to churches, and illustrated on two example cases. The same procedure can be used as the basis of a statistical extrapolation aimed at evaluating the probability distributions of collapse and damage among monumental buildings that are similar with regard to both the macroelement typologies and the logical diagram.