Deformation related to orogenic collision has been investigated along a complete crustal section exposed throughout the Sardinian Variscides, Italy. The dynamics of grain-scale deformation processes and palaeo-differential stress have been examined within three major shear zones (Rosas Shear Zone—RSZ, Baccu Locci Shear Zone—BLSZ and Giuncana Badesi Shear Zone—GBSZ) developed at progressively deeper structural levels from the foreland to the inner zone during the D1 phase of shortening associated with Barrovian-type metamorphism. Microstructural analysis reveals that the overall strain in quartz-feldspathic and calc-mylonites results from a combination of and, possibly, competition between several deformation mechanisms. At the sub-greenschist level (RSZ), operating mechanisms are pressure-solution associated with grain boundary sliding. Dislocation creep is the dominant process at the greenschist level (BLSZ), although pressure-solution is still effective in zones of strain concentration. In the lower crust (GBSZ), deformation occurred in the range of 600–620°C and 0.7–0.9 GPa by a combination of dislocation creep and high-T diffusional processes. Differential stresses inferred from quartz grain-size and calcite twin piezometers decrease with increasing depth, as predicted by most common rheological models. Despite this general trend, the stress profile across each shear zone suggests a pronounced stress gradient towards the zone of maximum deformation, leading to an increase of strain-rate up to two orders of magnitude. The results of this regional study demonstrate that both stress and strain within orogenic wedges are localized rather than distributed, allowing the crust to deform coherently at different structural levels. Copyright © 2010 John Wiley & Sons, Ltd.