The Sierra de Mamil Choique calc-alkaline granite batholith, covering an area of 320 km2, serves as the key reference for Late Paleozoic magmatism in central-west Patagonia. It comprises I-type weakly to mildly peraluminous tonalites to granites (59.6–75.7%SiO2) displaying various deformational features. This paper presents a micro- and mesostructural study alongside temperature-pressure (T-P) constraints coupled with U-Pb zircon crystallization ages, as well as Ar-Ar and K-Ar mica ages, and mineral and whole-rock geochemistry. The older units (288 ± 1 Ma Cerro Mojón Monzogranite and 281 ± 2 Ma Huenchuquil Granodiorite), exhibit syn-kinematic banding and strong NW-SE foliation showing a transition from magmatic-sub magmatic to high-T subsolidus deformational features, such as parallel alignment of magmatic minerals, sub magmatic fractures, melt pockets, and chessboard subgrains in quartz. Quartz recrystallization by grain boundary migration is also observed. These microstructures developed concurrently with the regional D3 event that affected the Devonian metamorphic host. Their crystallization started at 8 Kbar and ∼ 790 °C within a thickened crust (LaN/YbN = 13–15, average). In contrast, the younger units (278 ± 2 Ma; Nahuelfil and Antinao Monzogranites) exhibit mainly magmatic deformation and display a NE-SW parallel alignment of mostly subhedral K-feldspar. A D4 deformation younger than 278 Ma, with a sigma 1 NW-SE (in plain view- horizontal) would have controlled the emplacement of Nahuelfil and Antinao Monzogranites. Younger zircon ages (ca 265 Ma) in the 278 Ma monzogranites would result from resetting due to the magmatic-hydrothermal alteration associated with the later magmatic pulse of leucogranites and pegmatites of the 267 ± 8 Ma (Rb-Sr WR isochron) La Pintada Leucogranites. These leucogranites were emplaced in an already thinner crust (LaN/YbN = 2.6 average). The latest magmatic activity is represented by two groups of pegmatitic bodies one from 265 ± 6 to 257 ± 3 Ma and a younger one of ca. 252–251 Ma (Ar-Ar and K-Ar muscovite cooling ages). All units share a common mafic source, but the younger units crystallized from melts at lower pressure and temperature (748–725 °C). The magmatism, involving crustal recycling, occurred at an active margin during a stage of thickened crust from 290 to 280 Ma, followed by gradual thinning after 280 Ma. This change in crustal thickness fits models proposing a continuous Permian subduction with a variable dip angle of the subducted slab along the southwestern margin of Gondwana.