Bayesian model calibration techniques are commonly employed in the characterization of nonlinear dynamic systems, as they provide a conceptual and effective framework to deal with model uncertainties, experimental errors and procedure assumptions. This understanding has resulted in the need to introduce a model discrepancy term to account for the differences between model-based predictions and real observations. Indeed, the goal of this work is to investigate model-driven seismic structural health monitoring procedures based on a Bayesian uncertainty quantification framework, and thus make relevant considerations for its use in the seismic structural health monitoring, focusing on masonry structures. Specifically, the Bayesian inference has been applied to the calibration of nonlinear hysteretic systems to both provide: (i) most probable values (MPV) of the parameters following the calibration; and (ii) estimates of the model discrepancy posterior distribution. The effect of the model discrepancy in the calibration is first illustrated recurring to a single degree of freedom using a Bouc–Wen type oscillator as a numerical benchmark. The model discrepancy is then introduced for calibrating a reference nonlinear Bouc–Wen model derived from real data acquired on a monitored masonry building. The main novelty of this study is the application of the framework of uncertainty quantification on models representing data measured directly on masonry structures during seismic events.