Assessing the geochemical signature and the role of fluids in a key Variscan detachment zone demonstrates the link between crustal deformation, thermo-mechanical events and Variscan mineralization. We document meteoric fluid infiltration into the ductile segment of the Late-Carboniferous Quiberon detachment zone (QDZ), when synkinematic muscovite and tourmaline crystallized and equilibrated with deuterium-depleted surface-derived fluids during high-temperature deformation. Titanium-in-muscovite thermometry supported by microstructures indicate that syntectonic isotope exchange between fluids and hydrous minerals occurred above 500 °C. 40Ar/39Ar muscovite data (∼319–∼303 Ma) and U(–Th)/Pb geochronology on zircon, monazite and apatite (∼318–∼305 Ma) from syntectonic leucogranites together with microstructural and geochemical (U and REE contents) data suggest that meteoric fluid-rock-deformation interaction started at ∼320 Ma and played a major role in leaching uranium at ∼305 Ma. U–Th/Pb data (∼330–∼290 Ma) from migmatites located below the QDZ strengthen the idea that meteoric fluid infiltration, detachment activity, syntectonic leucogranite emplacement and migmatization were coeval and allowed the development of a sustained hydrothermal system.