The paper presents the development of a model for the fatigue resistance of brick masonry under compression. The model takes into account the random nature of the fatigue strength phenomena and, as a consequence, proposes different model parameters as a function of the desired probability level. The model, based on a Weibull distribution, has been calibrated with the still limited experimental data on brick masonry under high cycle compression loading. Very good correlation is obtained. The results show that there is a clear trend of the experimental data to follow the Weibull distribution. It is also shown how the fatigue resistance of brick masonry is not only dependent on the magnitude of the stress cycles, but also on the magnitude of the minimum stress level. The paper also shows how the proposed model can be used in the reliability-based assessment of the fatigue performance of existing masonry arch bridges. Either the nominal probability of failure (reliability index) to fatigue or the remaining service life with a predefined probability level for an existing bridge can be predicted with the proposed method.