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U-Pb and Hf zircon (sensitive high-resolution ion microprobe -SHRIMP- and laser ablation-inductively coupled plasma-mass spectrometry -LA-ICP-MS-), Ar/Ar hornblende and muscovite, and Rb-Sr whole rock-muscovite isochron data from the mylonites of the Sarandí del Yí Shear Zone, Uruguay, were obtained in order to assess the tectonothermal evolution of this crustal-scale structure. Integration of these results with available kinematic, structural, and microstructural data of the shear zone as well as with geochronological data from the adjacent blocks allowed to constrain the onset of deformation along the shear zone at 630-625 Ma during the collision of the Nico Pérez Terrane and the Río de la Plata Craton. The shear zone underwent dextral shearing up to 596 Ma under upper to middle amphibolite facies conditions, which was succeeded by sinistral shearing under lower amphibolite to upper greenschist facies conditions until at least 584 Ma. After emplacement of the Cerro Caperuza granite at 570 Ma, the shear zone underwent only cataclastic deformation between the late Ediacaran and the Cambrian. The Sarandí del Yí Shear Zone is thus related to the syncollisional to postcollisional evolution of the amalgamation of the Río de la Plata Craton and the Nico Pérez Terrane. Furthermore, the obtained data reveal that strain partitioning and localization with time, magmatism emplacement, and fluid circulation are key processes affecting the isotopic systems in mylonitic belts, revealing the complexity in assessing the age of deformation of long-lived shear zones