A careful petrologic analysis of mylonites’ mineral assemblages is crucial for a thorough comprehension of the rheologic behaviour of ductile shear zones active during an orogenesis. In this view, understanding the way new minerals form in rocks sheared in a ductile manner and why relict porphyroblasts are preserved in zones where mineral reactions are generally supposed to be deformation-assisted, is essential. To this goal, the role of chemical potential gradients, particularly that of H2O (µH2O), was examined here through phase equilibrium modelling of syn-kinematic mineral assemblages developed in three distinct mylonites from the Calabria polymetamorphic terrane. Results revealed that gradients in chemical potentials have effects on the mineral assemblages of the studied mylonites, and that new syn-kinematic minerals formed in higher-µH2O conditions than the surroundings. In each case study, the banded fabric of the mylonites is related to the fluid availability in the system, with the fluid that was internally generated by the breakdown of OH-bearing minerals. The gradients in µH2O favoured the origin of bands enriched in hydrated minerals alternated with bands where anhydrous minerals were preserved even during exhumation. Thermodynamic modelling highlights that during the prograde stage of metamorphism, high-µH2O was necessary to form new minerals while relict, anhydrous porphyroblasts remained stable in condition of low-µH2O even during exhumation. Hence, the approach used in this contribution is an in-depth investigation of the fluid-present/-deficient conditions that affected mylonites during their activity, and provides a more robust interpretation of their microstructures, finally helping to explain the rheologic behaviour of ductile shear zones.