This paper integrates new field observations to summarize the evolution of the 37–39°S segment of the Andean margin during the Neogene period. The western Neuquén Andes represent a transitional segment between the high, broad Central Andes and the low, narrow Patagonian Andes. The Main Cordillera at this latitude was uplifted between 11 and 6 Ma. Since then, extension and transtension has dominated the area. South of 38°S, deformation concentrates along the Liquiñe-Ofqui fault zone, a crustal-scale dextral strike-slip system that accommodates part of the margin-parallel component of oblique subduction. The architecture of the volcanic arc is strongly controlled by this fault zone. We differentiate four main tectonic phases: (1) late Oligocene–middle Miocene extension and development of a segmented intra-arc continental rift basin and broad volcanic zone; (2) late Miocene shortening, resulting in uplift, exhumation, and inversion of the former basins and a volcanic gap in the Main Cordillera; (3) Pliocene–early Pleistocene extension of the orogenic structure, reestablishment of the volcanic arc, and transtension along the intra-arc zone; and (4) late Pleistocene–Holocene narrowing of the arc and localized extension-transtension along the axial intra-arc zone. In the Central Andes, shortening has been more or less continuous since the Miocene, whereas in the Neuquén Andes, shortening stopped at ca. 6 Ma, probably related to the increase of the slab angle triggering the extension of the former orogenic structure and the onset of arc-parallel strike-slip faulting. The episodic evolution and migration of volcanism are related to changes in dip of the subducting plate.