The Andean foreland is divided into morphotectonic provinces characterized by diverse deformation styles and seismogenic behavior partially stemming from distinct geological histories that preceded the current phase of subduction. The transition between the high Andes and the eastern foreland is exposed to numerous natural hazards and contains critical economic infrastructure, yet we know relatively little about regional active tectonics due to few geophysical investigations. Here we use waveforms collected during a 15-month-long seismic network deployment in the Santa Bárbara System (SBS) of northwest Argentina following the 2015 Mw 5.7 El Galpón earthquake to determine the distribution and magnitude of local earthquakes, obtain a regional 1D seismic velocity model, and improve our overall understanding of SBS neotectonics. Of the nearly 1200 recorded earthquakes, ~700 occurred in the crust with half of the moment release associated with events deeper than 25 km. The depth extent of seismicity supports the notion that the SBS upper and middle crust are homogeneous and that the lower crust is composed of granulites. These conditions likely formed during Paleozoic mountain building and Salta Rift-related Cretaceous magmatism, which dehydrated the crust. We find no clear indications that a shallow, low-angle detachment fault inferred to have been active during Cretaceous rifting exerts a strong control on modern deformation in contrast to the active décollement beneath the adjacent fold-and-thrust belt of the Subandes to the north. It remains unclear how active, inverted normal faults in the SBS shallow crust connect to the deeper zones of seismicity.