We present a regional-scale study combining field, seismic, and limited borehole information to analyze the structural characteristics of the thrust belt front of the western Central Andes at 21°S. This region, located in northern Chile, consists of the easternmost part of the Coastal Cordillera, the Pampa del Tamarugal, and the western Domeyko Cordillera (or Chilean Precordillera). On the surface, a series of N–S-oriented folds alternating between monoclines and narrow anticline and syncline folds containing Mesozoic, Upper Cretaceous, and Cenozoic rocks form part of the main structural styles, which are frequently bound by west-verging reverse faults that form the basement of the deeper structural levels of the upper crust. The interpretation of a regional seismic grid composed of N–S, NE–SW, and WNW–ESE-oriented 2-D seismic profiles revealed the presence of several blind west-verging inversion anticlines that define the orogenic front of the Central Andes at this latitude. These anticline folds are related to the partial and/or total positive reactivation of ancient east-dipping Jurassic normal basement faults bounding half-graben structures and sub-basins developed within the Tarapacá Basin. Our results suggest that the thrust belt front in this region is preferably located under the Pampa del Tamarugal, and not along the topographic culmination of the western Precordillera as traditionally proposed. New tectonic restorations of 2-D structural models suggest that, during tectonic inversion, between 3 and 4 km of crustal shortening were accommodated by vertical motion along the inverted normal faults. The presence of Upper Cretaceous synorogenic deposits covering the Jurassic syn-rift deposits on the inversion anticlines indicates that both basin inversion and formation of the western thrust belt front began during the Late Cretaceous, and not during the Eocene “Incaic” tectonic phase as previously suggested by regional studies developed in the area.