This paper discusses the effects of different modeling strategies on the simulated global response of masonry buildings with timber diaphragms under earthquake excitation. The benchmark for this study was provided by a unidirectional dynamic shake-table test on a three-story, half-scale natural stone masonry building aggregate, incorporating the main architectural and structural features of the historical center of Basel (Switzerland). The global response of the specimen was simulated through nonlinear static analyses using an equivalent frame approach, with nonlinear macroelements for masonry members and linear orthotropic membranes for diaphragms. Three modeling strategies were followed. In the first case, given their low stiffness, the timber diaphragms were considered infinitely flexible and single-wall 2D models were analyzed in the shaking direction. The second option consisted of a 3D model with walls in both directions and finite-stiffness diaphragms, however neglecting the out-of-plane overturning response of walls. A third, unconventional modeling strategy was adopted, to implement explicitly the out-of-plane stiffness of walls orthogonal to the shaking direction through a particular combination of equivalent frames and membranes. Numerical backbone curves and lateral displacement envelopes were compared to experimental counterparts, proving satisfactorily accurate even when diaphragm and out-of-plane wall stiffnesses were neglected.