The Frontal Cordillera in northern Chile is located over the flat-slab subduction segment of the Central Andes. This tectonic province is characterized by a thick-skinned structural style showing evidence of tectonic inversion and basement-involved compressive structures. Field data, U-Pb geochronological and apatite fission track data were used to unravel partially the tectonic history of the area. Previous U-Pb ages of synorogenic deposits exposed on the flanks of basement-core anticlines indicate that Andean deformation started probably during Late Cretaceous with the tectonic inversion of Triassic and Jurassic half-grabens. New U-Pb ages of the synorogenic Quebrada Seca Formation suggest that this deformation continued during Paleocene (66-60 Ma) with the reverse faulting of pre-rift basement blocks. The analysis of new apatite fission-track data shows that a rapid and coeval cooling related to exhumation of the pre-rift basement blocks occurred during Eocene times. This exhumation event is interpreted for first time in the Chilean Frontal Cordillera and it could have occurred simultaneously with the propagation of basement-involved structures. The age of this exhumation event coincides with the Incaic orogenic phase, which is interpreted as the most important to the Central Andes in terms of shortening, uplift and exhumation.