The central Apennines are among the most seismically active sectors of the central Mediterranean region, as testified by the recent sequence of Mw >6 earthquakes (L’Aquila Mw 6.3, 6 April 2009; Amatrice Mw 6.2, 24 August 2016), that struck the region. Although many recent studies have focused on the recent history of the active and seismogenic faults, due to the poor understanding on the age of the fault-bounded intermontane basins and on the early stage of their continental deposition, less is known about the faults’ long-term behavior. To try to fill this knowledge gap, we analyzed a long sediment core (230 m depth, Castelnuovo 1 borehole; CN-1) recovered from the infill of the Plio-Pleistocene tectonically active L’Aquila Basin (Paganica−San Demetrio−Castelnuovo [PSC] Sub-basin) by employing 40Ar/39Ar dating, magnetostratigraphy, multiproxy paleoclimatic data (palynological analyses, pollen temperature index and clumped isotopes), and astrocyclostratigraphy. Combining the results from the CN-1 pollen record, 40Ar/39Ar dating of a tephra (1.77 ± 0.15 Ma), and magnetostratigraphy of the CN-1 sediment core, we can refer the longest normal polarity interval (N3) to the Olduvai subchron, which we use to constrain the CN-1 age model. Moreover, spectral analysis of the CN-1 calcimetry data series shows the presence of 13 obliquity-modulated cycles, resulting in an age of ca. 1490 ka for the top of the core and an age of ca. 2027 ka for its base. This time span encompasses Marine Isotopic Stages (MIS) 50−75. The occurrence of lacustrine ostracod fauna since the lowermost portion of the CN-1 core points to the presence in the PSC Sub-basin, already at 2 Ma, of a well-developed intermontane lake. Both pollen assemblages and clumped isotopes show warm-to-cold climate changes along the CN-1 sediment core, with clumped-isotope−derived temperatures of the lake waters of 15.4 ± 1.6 °C (MIS 53) and 11.5 ± 1.3 °C (MIS 52), whereas temperatures of 21 ± 1.7 °C and 15.6 ± 1.7 °C correspond respectively to MIS 67 and MIS 64. The PSC Sub-basin shows a complex subsurface architecture, with highs and depocenters showing maximum thickness of the lacustrine deposits up to 510−450 m. Considering that the CN-1 age model points to a sedimentation rate of 0.3 mm/yr for the deep lacustrine deposits, the onset of the continental sedimentation in the L’Aquila intermontane basin started at ca. 3.2−3.0 Ma. This post-orogenic extensional domain responsible for the onset and subsequent development of the L’Aquila intermontane basin is still active, representing an archive of ∼3 m.y. of continued crustal extension from one of the most seismically active sectors of the central Mediterranean region.