Study of the tectonically active L’Aquila Basin offers new insights into both the creation of the extensional intermontane basins of the central Apennines of Italy and their tectono-sedimentary evolution through time. The combination of large mammal remains, ostracods, molluscs, Mousterian tools, and 14C dating allows better definition of the onset and stratigraphic evolution of the L’Aquila Basin. Interpretation of a seismic reflection profile and well-log data allow evaluation of the subsurface setting of this sedimentary basin and its tectono-sedimentary evolution. The occurrence of a wedge-shaped seismic unit at the base of the basin sedimentary succession defines the first phase of basin fill during a late Piacenzian–Gelasian synrift stage. Activity along the main fault of the extensional fault system responsible for the onset and subsequent development of the western sector of the L’Aquila Basin (L’Aquila–Scoppito subbasin) migrated from southwest to northeast, reaching the presently active Mount Pettino normal fault only in the late Pleistocene–Holocene. The onset of sedimentation in the L’Aquila Basin was synchronous with the onset in the Tiberino Basin, and so the idea that these extensional intermontane basins become progressively younger from the Tyrrhenian toward the Adriatic side of the central Apennines is rejected. In the northern and central Apennines, only two major syndepositional extensional domains can be recognized: a late Miocene rifting area, which includes all the late Miocene extensional basins in Tuscany, and a late Pliocene to earliest Pleistocene rifting area, which possibly includes all the intermontane basins from the Tiberino Basin to the Sulmona Basin. The different time gaps between compressional and extensional deformation at any given locality in the central Apennines could indicate a partial decoupling of processes responsible for the migration of shortening and extension toward the foreland. Diachroneity between the eastward migration of shortening in the foreland and extension in the inner part of the orogen supports the notion that the central Apennines were created as a result of a partially decoupled collision zone. Study of the onset of the central Apennine extensional intermontane basins, together with their seismic activity, indicates that the central Apennine postorogenic extensional domain represents an archive of ∼3 m.y. of continued crustal extension. These findings help to refine models of the long-term extensional rate of the central Apennines, and they provide a basis for more reliable seismotectonic models for one of the most seismically active sectors of the central Mediterranean area.