This contribution focuses on modeling procedures to describe damage mechanisms evolving in masonry structures under mechanical and environmental actions. After introducing the proposed protocol developed to analyze the overall mechanical response of masonry historical constructions, a macromechanical constitutive model coupling damage and plasticity effects is presented in detail. Two case studies are analyzed, concerning a masonry façade subjected to tunneling-induced settlements and the Tortona town hall, selected as real cases to evaluate the effects of environmental and man-made loads on the structural response of buildings with historical relevance.