The work presents the inter-disciplinary multi-year project focused on the permanent seismic monitoring of a historical structure, the Basilica S. Maria di Collemaggio, by means of an advanced wireless sensor network. Considered among the architectural masterpieces of the Italian Romanesque, the structural behaviour of the monumental masonry church is strongly debated after the heavy damages and the partial collapse that occurred during the 2009 L’Aquila earthquake. From the perspective of information technology, critical issues in the wireless data acquisition and communication are analysed. The sensor network design, deployment and performance are discussed with respect to the high-demanding service requirements—as well as the non-negligible management costs—specifically related to the long-term monitoring of a monumental masonry structure in a seismic area. From the perspective of experimental signal analysis, the acceleration data collected during a 3-year period of seismic monitoring are analysed in the frequency and time domains. The results allow the clear detection of complex interactions between the masonry structures and some of the temporary protective installations. Stochastic subspace identification procedures are applied, with critical analysis of their effectiveness in the assessment of reliable modal models from the building response to real seismic events. Finally, the robustness of the modal identification obtained from the structural responses to different near- and far-field micro-earthquakes is discussed, with the aid of numerical models of the damaged and protected church configuration