Crystallisation-driven differentiation is one fundamental mechanism proposed to control the compositional evolution of magmas. In this experimental study, we simulated polybaric fractional crystallisation of mantle-derived arc magmas. Various pressure–temperature trajectories were explored to cover a range of potential magma ascent paths and to investigate the role of decompression on phase equilibria and liquid lines of descent (LLD). Fractional crystallisation was approached in a step-wise manner by repetitively synthesising new starting materials chemically corresponding to liquids formed in previous runs. Experiments were performed at temperatures ranging from 1140 to 870 °C with 30 °C steps, and pressure was varied between 0.8 and 0.2 GPa with 0.2 GPa steps. For most fractionation paths, oxygen fugacity (fO2) was buffered close to the Ni-NiO equilibrium (NNO). An additional fractionation series was conducted at fO2 corresponding to the Re-ReO2 buffer (RRO ≈ NNO+2). High-pressure experiments (0.4–0.8 GPa) were run in piston cylinder apparatus while 0.2 GPa runs were conducted in externally heated pressure vessels. Resulting liquid lines of descent follow calc-alkaline differentiation trends where the onset of pronounced silica enrichment coincides with the saturation of amphibole and/or Fe–Ti–oxide. Both pressure and fO2 exert crucial control on the stability fields of olivine, pyroxene, amphibole, plagioclase, and Fe–Ti–oxide phases and on the differentiation behaviour of arc magmas. Key observations are a shift of the olivine–clinopyroxene cotectic towards more clinopyroxene-rich liquid composition, an expansion of the plagioclase stability field and a decrease of amphibole stability with decreasing pressure. Decompression-dominated ascent trajectories result in liquid lines of descent approaching the metaluminous compositional range observed for typical arc volcanic rocks, while differentiation trends obtained for cooling-dominated trajectories evolve to peraluminous compositions, similar to isobaric liquid lines of descent at elevated pressures. Experiments buffered at RRO provide a closer match with natural calc-alkaline differentiation trends compared to fO2 conditions close to NNO. We conclude that decompression-dominated fractionation at oxidising conditions represents one possible scenario for arc magma differentiation. © 2021, The Author(s).