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This paper presents a novel hybrid-based methodology devoted to develop urban fragility curves and damage probability matrices to predict likelihood seismic damage scenarios for small and medium Italian urban centres, considering URM buildings only. The concept of urban fragility curve consists of a single curve mean-representative of the seismic fragility of an entire area accounting for the combinations of building classes and their percentage, then they differ from those typological. The methodology has been developed with reference to Rocca di Mezzo, a small Italian urban centre located in the central Apennine area, Italy. Based on CarTiS inventory, building classes have been firstly recognized and urban fragility curves, representative for damage scenarios at Ultimate Limit State, developed. To predict damage scenarios from low to high-intensity earthquakes, an approach to define multi-damage urban fragility curves and damage probability matrices has been also presented. To this aim, a damage scale suffered by building classes has been defined by converting the final outcomes of the AeDES form (used in Italy for post-earthquake surveys) in the damage levels provided by the European Macroseismic Scale (EMS98). Data coming from urban fragility curves have been compared with the actual damage scenario recorded in Rocca di Mezzo after the 2009 L’Aquila’s earthquake, in terms of both peak-ground acceleration and Mecalli-Cancani-Sieberg scale. The achieved results showed a good accordance between theoretical predictions and actual damage scenarios, coherent also with the damage scenarios occurred in other Italian historical centres hit by severe earthquakes over the years. Thus, the methodology can provide a first important indicator to support the development of emergently plans devoted to identify priority of interventions in such areas particularly vulnerable with respect to others.