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Andesitic arc volcanism is the most common type of subduction-related magmatism on Earth. How these melts are generated and under which conditions they evolve towards silica-rich liquids is still a matter of discussion. We have performed crystallization experiments on a representative andesite sample from the Upper Scoriae 1 (USC-1) eruption of Santorini (Greece) with the aim of understanding such processes. Experiments were performed between 1000 and 900 °C, in the pressure range 100–400 MPa, at fO2 from QFM (quartz–fayalite–magnetite) to NNO (nickel–nickel oxide) + 1·5, with H2Omelt contents varying from saturation to nominally dry conditions. The results show that the USC-1 andesitic magma was generated at 1000 °C and 12–15 km depth (400 MPa), migrated to shallower levels (8 km; 200 MPa) and intruded into a partially crystallized dacitic magma body. The magma cooled to 975 °C and generated the phenocryst assemblage and compositional zonations that characterize the products of this eruption. An injection of basaltic magma problably subsequently triggered the eruption. In addition to providing the pre-eruptive conditions of the USC-1 magma, our experiments also shed light on the generation conditions of silica-rich magmas at Santorini. Experimental of runs performed at fO2 ∼ NNO + 1 (± 0·5) closely mimic the compositional evolution of magmas at Santorini whereas those at reduced conditions (QFM) do not. Glasses from runs at 1000–975 °C encompass the magma compositions of intermediate-dominated eruptions, whereas those at 950–900 °C reproduce the silicic-dominated eruptions. Altogether, the comparison between our experimental results and natural data for major recent eruptions from Santorini shows that different magma reservoirs, located at different levels, were involved during highly energetic events. Our results suggest that fractionation in deep reservoirs may give rise to magma series with a tholeiitic signature whereas at shallow levels calc-alkaline trends are produced.