The Liquiñe-Ofqui fault zone (LOFZ) is a long-lived, margin-parallel, intra-arc megastructure, which has played a significant role in both orogenic growth and magmatism during the Late Cenozoic. The LOFZ has been regarded as a Late Miocene-Pliocene dextral strike-slip fault zone within a bulk transpressional setting. Nevertheless, little geologic and morphological evidence exists for Quaternary right-lateral offsets. In contrast, vertical separation is the most outstanding feature observable along the master faults. The river network also shows local discontinuities (sinuosity, stream power index) where cut by these first-order faults. In humid climates, topographic equilibrium should be rapidly restored; therefore, at least part of the vertical displacement should be Holocene. Vertical movements can be caused by tectonic forces but are also enhanced by the postglacial isostatic rebound. The latter would have been intense during the Quaternary and especially after the Last Glacial Maximum (i.e., < ca. 14 ka) in the Southern Andes between 38° and 46°S. A consistent Quaternary NE-oriented maximum horizontal stress accompanies both compressional and transpressional tensors along the entire volcanic arc, which supports the argument that part of the vertical displacement could be tectonic in origin. Therefore, competing transpressional and compressional regimes, with both strike-slip and vertical displacement, occur along the entire intra-arc zone, and are spatially and causally related to a wide variety of volcanic outspurs. Compression and transpression can alternate along the intra-arc fault systems (by shifting σ2 and σ3; σ1 remaining constant) because of local or regional factors such as inherited discontinuities and/or variations of the angle between the convergence vector and the continental margin trend. The shifting between σ2 and σ3 should be common in highly oblique subduction zones, which develop "pure shear-dominated" strain regimes. Whatever the driving mechanism of vertical displacements, the most primitive Holocene basaltic magmas were erupted along the LOFZ master faults, where the vertical offsets are more clearly distinguished. At the regional scale, arc volcanism would be sustained by flux melting in the asthenosphere and magma ascent controlled by the bulk transpressional regime. Instead, sporadic vertical adjustments along the LOFZ, either by tectonic and/or climatic processes, would trigger monogenetic volcanism after induced decompressional melting. Thus, volcanic and orogenic processes are coupled and should be considered for understanding the global arc architecture and coeval relief building.