Historic masonry towers are among the most vulnerable components of the built cultural heritage owing to their high slenderness, material degradation, geometric imperfections, and limited tensile strength. In the province of Ferrara (Northern Italy), several historic towers exhibit significant out-of-plumbness caused by long-term foundation settlements, while some sustained structural damage during the 2012 Emilia–Romagna earthquake sequence. Assessing their seismic safety is particularly challenging because existing inclinations modify the stress state and strongly influence the structural response under earthquake loading. This study presents a numerical methodology for the seismic vulnerability assessment of five representative historic masonry towers located in the Ferrara area. The proposed approach is based on simplified three-dimensional numerical models that reproduce the global structural behavior with limited computational effort, making them suitable for practical engineering assessment. The models incorporate the geometry, existing inclination, and mechanical properties of each tower and are subjected to gravity loading and code-based seismic actions corresponding to different seismic hazard scenarios. The numerical results are systematically compared with the assessment procedures and safety verifications prescribed by the current Italian seismic code, allowing the applicability and limitations of simplified assessment approaches to be critically evaluated. The structural response is evaluated through engineering demand parameters, including lateral displacements, stress distributions, and demand-to-capacity ratios, enabling the identification of the governing failure mechanisms and the most vulnerable structural configurations. The comparative analysis of the five case studies highlights the influence of tower inclination, geometry, and construction characteristics on the seismic response, revealing significant variability in structural performance and code compliance. The proposed methodology provides a practical and computationally efficient framework for the preliminary seismic assessment of historic masonry towers, supporting vulnerability screening and the prioritization of detailed investigations for existing heritage structures.