Unreinforced masonry (URM) buildings without box-like behavior and undergoing seismic actions are particularly vulnerable to out-of-plane (OOP) mechanisms. These may involve the partial or total collapse of walls with severe implications in terms of hazard to people, structures and cultural heritage. In this paper, an advanced macro-block model, accounting for interlocking effects between walls and using the kinematic approach of limit analysis, is used to calculate the activation load factors in a single-story URM building. Two classes of local mechanisms are considered: the rocking-sliding (simple and compound rocking of the façade, rocking corner) and the horizontal flexure mechanisms. Employed formulations take into account in-plane shear forces and torsion-shear-bending interactions, while the geometry of the moving macro-blocks is considered as a variable in the minimization of the load factor activating the motion. The aim of the paper is to investigate the role played by geometrical parameters (façade and unit dimensions), mechanical characteristics (friction coefficient) and static thrusts of the roof on the activation load factors. In particular, a sensitivity analysis of the load factors is carried out for each local mechanism, in order to quantify what weight can be attributed in the results to each variable parameter. The final perspective of the presented study on the single-story URM building is to understand which variable input can mostly influence the onset of a local mechanism in order to support more complex analyses extended to multi-story URM buildings.