Tectonic development of the Andean Cordillera has profoundly changed the topography, climate, and vegetation patterns of the southern central Andes. The Cenozoic Bermejo Basin in Argentina (~30°S) provides a key record of thrust belt kinematics and paleoclimate south of the high-elevation Puna Plateau. Ongoing debate regarding the timing of initiation of upper plate shortening and Andean uplift persists, precluding a thorough understanding of the earlier tectonic and climatic controls on basin evolution. We present new sedimentology, detrital geochronology, sandstone petrography, and subsidence analysis from the Bermejo Basin that reveal siliciclastic-evaporative fluvial and lacustrine environments prior to the main documented phase of Oligocene-Miocene shortening of the Frontal Cordillera and Argentine Precordillera. We report the first radiometric dates from detrital zircons collected in the Ciénaga del Río Huaco Formation, previously mapped as Permian, that constrain a Late Cretaceous (~95–93 Ma) maximum depositional age. Provenance and paleocurrent data from these strata indicate that detritus was derived from dissected arc and cratonic sources in the north and northeast. Detrital zircon U-Pb ages of ~37 Ma from the overlying red beds suggest that foredeep sedimentation began by at least the late Eocene. At this time, sediment dispersal shifted from axial southward to transversal eastward from the Andean Arc and Frontal Cordillera. Subsidence analysis of the basin fill is compatible with increasing tectonic deformation beginning in Eocene time, suggesting that a distal foredeep maintained fluvial connectivity to the hinterland during topographic uplift and unroofing of the Frontal Cordillera, prior to Oligocene-Miocene deformation across the Precordillera.