This paper focuses on the reprocessing of seismic reflection profiles, aeromagnetic and seismicity data, to locate and characterize the Ota-Vila Franca de Xira-Lisbon-Sesimbra fault zone. The studied structure is sited in the Lower Tagus Valley, an area with over 2 million inhabitants, that has experienced historical earthquakes causing many casualties, serious damage and economical losses (e.g. 1531 January 26 and 1909 April 23 earthquakes), whose tectonic sources are mostly unknown. The fault zone trends NNE-SSW to N-S, is located near the eastern border of the Mesozoic Lusitanian Basin and partially delimits the Lower Tagus Cenozoic Basin at the west, mostly hidden under the Cenozoic sedimentary fill. According to the data presented here, the normal structures that compose the fault zone were reactivated in Cenozoic times, with positive inversion and the development of splays towards the east. The fault zone shows three distinct segments with different behaviour, in conformity with their various orientations relative to the NW-SE maximum compressive stress. The northern segment splays into a series of NNE-SSW oriented, east verging, imbricate thrusts, which merge to the west into a major reverse fault that resulted from the tectonic inversion of the former normal fault bordering the Mesozoic Lusitanian Basin in this area—the well known Ota (or Pragança) fault. The central segment corresponds to the approximately 20 km long outcropping Vila Franca de Xira fault, which suffered a maximum degree of inversion. The southern segment extends for ∼45 km, crossing Lisbon and the Setúbal Península at depth until approximately Sesimbra (probably continuing offshore), with an N-S trend and distinct geometry. South of Vila Franca de Xira, there is evidence for a WSW-ENE fault located at depth, producing a righ-lateral stepover on the major structure and splitting the central from the southern segment. We hypothesize that this obliquely trending fault is a possible source of the 1909 Benavente earthquake.