In northwestern Argentina, mid-Pleistocene out-of-sequence thrusting further disrupted the Andean foreland, giving rise to the Lerma piggyback basin within the Eastern Cordillera. Emergent topography along the eastern edge of the basin, as well as in its interior, interfered with preexisting eastward-flowing river courses. In the northern part of the Lerma basin, rivers temporarily incised across the new topography, yielding wind and water gaps, and in places preserving straths with treads tilted upstream, revealing their tectonic origin. Application of Hack’s law shows correspondence between the active and the abandoned channel profiles. Bed profiles of wind gaps are distinct from those of nearby consequent streams. Defeated and deflected northern streams coalesced into a trunk stream, which maintained an open channel across the eastern bounding ranges. River defeat may have been related to rain shadowing by the growing topographic barrier and retention of easterly derived moisture outside the Lerma basin. In the southern Lerma basin, river courses were not generally capable of sustaining active water gaps. Instead, they were deflected southward, and their discharges fed ancient Lake Lerma. Lake expansion ensued until water level reached a structural low, through which lake waters outflowed from the basin and subsequently incised across the eastern bounding ranges. The relative success of northern rivers in incising across the rising topographic barrier is mainly attributed to their greater channel gradients at the point of incision, combined with high rainfall levels. Longitudinal channel profiles show that rivers in the northern Lerma basin had approached their base level of erosion before uplift of the eastern bounding ranges. After this disturbance, the system continues to approach a new base level of erosion, modified by sediment aggradation within the basin. Speculatively, mid-Pleistocene out-of-sequence thrusting is attributed to basement uplift in the distal foreland.