Understanding the relationships between sedimentation, tectonics and magmatism is crucial to defining the evolution of orogens and convergent plate boundaries. Here, we consider the lithostratigraphy, clastic provenance, syndepositional deformation and volcanism of the Almagro-El Toro basin of NW Argentina (24°30′ S, 65°50′ W), which experienced eruptive and depositional episodes between 14.3 and 6.4 Ma. Our aims were to elucidate the spatial and temporal record of the onset and style of the shortening and exhumation of the Eastern Cordillera in the frame of the Miocene evolution of the Central Andes foreland basin. The volcano-sedimentary sequence of the Almagro-El Toro basin consists of lower red floodplain sandstones and siltstones, medial non-volcanogenic conglomerates with localised volcanic centres and upper volcanogenic coarse conglomerates and breccia. Coarse, gravity flow-dominated (debris-flow and sheet-flow) alluvial fan systems developed proximal to the source area in the upper and medial sequence. Growing frontal and intrabasinal structures suggest that the Almagro-El Toro portion of the foreland basin accumulated on top of the eastward-propagating active thrust front of the Eastern Cordillera. Synorogenic deposits indicate that the shortening of the foreland deposits was occurring by 11.1 Ma, but conglomerates derived from the erosion of western sources suggest that the uplift and erosion of this portion of the Eastern Cordillera has occurred since ca.12.5 Ma. An unroofing reconstruction suggests that 6.5 km of rocks were exhumed. A tectono-sedimentary model of an episodically evolving thick-skinned foreland basin is proposed. In this frame, the NW-trending, transtensive Calama–Olacapato–El Toro (COT) structures interacted with the orogen, influencing the deposition and deformation of synorogenic conglomerates, the location of volcanic centres and the differential tilt and exhumation of the foreland.