The thick-skinned Sierras Pampeanas morphotectonic domain of western and northwestern Argentina (27°S–33°S) is characterized by reverse-fault–bounded basement blocks that delimit internally deformed, Neogene sedimentary basins. Foreland-basin evolution in this part of the Andes is still not very well understood. For example, challenging questions exist as to how thick-skinned deformation develops, if there are distinct spatiotemporal trends in deformation and exhumation, how such deformation styles influence sedimentation patterns, and whether or not broken foreland basins are related to regional plate-tectonic processes, such as flat-slab subduction. The Fiambala basin of the northwestern Sierras Pampeanas is the largest of several intermontane basins in the transition to the southern margin of the Puna Plateau. This basin preserves a thick continental Neogene sequence that provides information on the dynamics of thick-skinned deformation and resulting sedimentation. The Fiambala basin contains ~4 km of fluvial-alluvial sedimentary rocks that comprise the Tamberia, Guanchin, and Punaschotter Formations. U-Pb geochronology of ashes intercalated within the Fiambala stratigraphic sequence demonstrates that these sedimentary rocks are late Miocene to Pliocene (8.2 ± 0.3 Ma to 3.05 ± 0.4 Ma) in age. Sedimentology and provenance data indicate that the source of the Tamberia Formation was located to the west of the modern western basin-bounding range. The Guanchin and Punaschotter Formations record input from local sources, including the modern basin-bounding range to the west and the southern Puna Plateau to the north, suggesting reorganization of the catchment area at ca. 5.5 Ma. The coarsening-upward trends recorded by the fluvial Tamberia and Guanchin Formations indicate enhanced tectonics and relief during sedimentation. The Punaschot-ter conglomerates record alluvial-fan sedimentation and local sources. Fault kinematic data document a contractional regime, characterized by E-W and NE-SW shortening, active throughout the middle-late Miocene and Pliocene. Furthermore, a comparison between the Fiambala basin and similar sedimentary basins in the Sierras Pampeanas (e.g., Bermejo foreland basin) and the Eastern Cordillera leads us to propose that the study area originally constituted an integral part of a continuous and more extensive foreland-basin system (thin-skinned) for much of its early history. Our data suggest coeval intrabasin deformation along strike from the Bermejo region northward to the Eastern Cordillera. The coeval change at ca. 6 Ma from a regional to more compartmentalized (thick-skinned) tectono-sedimentary environment in the regions adjacent to the Eastern Cordillera, the southern Puna margin, and other sectors within the Sierras Pampeanas domain may thus reflect a regional tectonic process related to flat subduction. Our data, combined with existing sedimentological and petrological evidence, imply that the passage from steep to flat subduction occurred synchronously from ~30°S to ~26°S.