On 26 September 1997, the town of Nocera Umbra, central Italy, was strongly hit by two nearby ML 5.6 and 5.8 earthquakes. The effects were particularly heavy in the historical part of the town, on the top of a 120-m-high hill. However, also modern zones along the Topino valley suffered severe damage with many partial collapse episodes. Aftershock recordings in different zones stressed the occurrence of large variations of the ground-motion strength within the town. These observations suggest that the spatially heterogeneous distribution of damage in Nocera Umbra should have been a combination of variations of both building vulnerability and ground shaking intensity within the town. We have identified six microzones characterized by different vulnerability and/or varying geological and topographical conditions. In each of them, the number of damaged houses is computed for vulnerability types A, B, and C according to the European Macroseismic Scale 1998 (EMS-98). This procedure yields a macroseismic intensity of VII–VIII on the hill in the historical part of the town. In this zone, the topography amplification has a limited extent while the quality of the construction materials is poor; the diffuse damage is then interpreted as an effect of the higher vulnerability of buildings in the historical zone. The other urbanized zones of Nocera Umbra are composed of more recent, less vulnerable buildings. In spite of the almost homogeneous building vulnerability, the observed damage grades show significant variations between the remaining five microzones. In particular, damage grades related to intensity as low as VI–VII were assessed for undisturbed Mesozoic limestone and stiff Cenozoic–Mesozoic marly sandstone zones, where aftershock seismograms show the smallest relative amplitudes. The highest damage grades (related to intensity VIII) were estimated for two zones, on the soft sediment deposits in the Topino River valley and on the fractured marly sandstone terrains within a 200-m-wide fault zone crossing the town of Nocera Umbra. Such an increment of one to two degrees in EMS intensity corresponds to a maximum spectral amplification of horizontal ground motion around 4 Hz that is as large as 20 on the soft sediment deposits and even larger within the fault zone.