The evaluation of the structural behaviour of iconic historic buildings represents one of the most current structural engineering research topics. However, despite the various research works carried out during recent decades, several issues still remain open. One of the most important aspects is related to the correct reconstruction of the complex geometries that characterise this type of construction and that influence structural behaviour, especially in the presence of the horizontal loads caused by seismic action. For these reasons, different techniques have been proposed based on the use of laser scanners, Unmanned Aerial Vehicles (UAVs), and terrestrial photogrammetry. At the same time, several analysis methods have been developed that include the use of linear and non-linear approaches. In this present paper, the seismic performance of the Santa Maria Novella basilica and Santa Maria di Collemaggio basilica (before the partial collapse due to the 2009 L’Aquila earthquake) were investigated in detail by means of several numerical analyses. In particular, a series of non-linear time history analyses (NTHAs) were carried out, as reported in the Italian Building Code. To represent the non-linear behaviour of the main structural elements, smeared cracking (CSC) constitutive law was adopted. The geometry of the structures was reconstructed from a complete laser scanner survey of the churches, in order to consider all the intrinsic irregularities that characterise the heritage buildings. Finally, a comparison between the structural behaviour of the two case studies was carried out, highlighting the differences and similar aspects, focusing on possible collapse mechanisms and the identification of the most critical structural elements represented, in both cases analysed, by the main pillars of the transept.