A multidisciplinary approach is used to investigate the structure of the southern Cretan margin, which is located in one of the most seismically active forearc regions in Europe. Bathymetric, seismic-reflection, and fault plane solution data were used to identify the main tectonic features on the margin, correlating their evolution with the main sedimentary sequences recognized on Crete. In contrast to the majority of forearc settings in the Pacific and Indian Oceans, southern Crete is a region of predominantly oblique movement above well-defined detachment zones. North-dipping thrust faults identified on seismic-reflection profiles reveal significant crustal shortening during the Miocene due to the westward propagation of the Hellenic fold-and-thrust system. In addition, east-dipping thrust faults rooted on top of pre-Neogene strata were also identified, but only a few of these thrusts affect Neogene to Holocene strata. Small-scale domes derived from evaporitic (Messinian) intrusions deform Pliocene–Quaternary strata. West- and east-dipping normal faults were also recognized within the Mesozoic and Cenozoic successions, and these are related to regional extension during forearc convergence. In such a setting, the fault-bounded continental slope of Crete effectively separates a region of uplift (Crete) from subsiding troughs to the south. Our work shows that structural segmentation at depth is complex, with multiple crustal levels recording contrasting styles of deformation and distinct moment-tensor solutions. This complexity derives from the oblique style of convergence recorded south of Crete, which reactivates distinct crustal levels depending on their rheology and relative degree of metamorphism inherited during Alpine compression. As a result, a strong correlation between seafloor morphology and transtensional movements is recorded in the upper 10–15 km of the crust, while transpression prevailed after the Serravallian below these depths.