The results of an integrated stratigraphic, structural, geophysical, and geochemical study reveal the presence of a crustal discontinuity in western Sicily that, at present, runs roughly N-S along a band from San Vito Lo Capo to Sciacca. The boundary between the two zones of this discontinuity is nearly orthogonal to the main thrust propagation of the Sicilian thrust-and-fold belt. The different Permian to Tertiary sedimentary evolution recorded by the two zones appears related to this discontinuity, with thick carbonate platforms in the western sector facing deepwater successions in the eastern one. The presence of Upper Triassic reefs, huge megabreccia bodies, and widespread submarine volcanisms along the transition zone suggests the presence of a long-lasting weakness zone. This zone has been reactivated episodically as transpressional and/or transtensional faults in relation to the different geodynamic stress acting in central Mediterranean area in different epochs. We speculate that this transition zone has represented a segment of the passive margin of the Ionian Tethys. During the Maghrebian convergence a different style of deformation has affected the two sectors floored by different sedimentary multilayers. The orthogonal-to-oblique differential convergence between the two sectors has resulted in right-lateral transpressional motions, leading to oblique thrusting of deepwater-derived thrusts onto platform-derived thrusts associated with clockwise rotations. The oblique convergence is still ongoing as demonstrated by the seismicity of the area, by the geothermal field with high mantle-derived helium fluxes and by the GPS measurements collected by different authors.