Santorini volcano in the Aegean region (Greece) is characterized by andesitic- to silicic-dominated explosive activity and caldera-forming eruptions, sourced from magmatic reservoirs located at various structural levels beneath the volcano. There is a good understanding of the silica-rich magmatism of the island whereas the andesite-dominated volcanism and the petrogenesis of the parental mafic magmas are still poorly understood. To fill this gap we have performed crystallization experiments on a representative basalt from Santorini with the aim of determining the conditions of differentiation (pressure, temperature, volatile fugacities) and the parental magma relationship with the andesitic eruptive rocks. Experiments were carried out between 975 and 1040°C, in the pressure range 100–400 MPa, fO2 from QFM to NNO + 3·5 (where QFM is quartz–fayalite–magnetite and NNO is nickel–nickel oxide), with H2Omelt contents varying from saturation to nominally dry conditions. The results show that basalt phenocrysts within the basalt crystallized at around 1040°C in a magma storage reservoir located at a depth equivalent to 200–400 MPa pressure, with 3–5 wt % dissolved H2O, and fO2 around QFM. Comparison with the xenocryst and phenocryst assemblages of the Upper Scoria 1 andesite shows that andesitic liquids are produced by fractionation of a similar basalt at 1000°C and 400 MPa, following 60–80 wt % crystallization of an ol + cpx + plag + Ti-mag + opx ± pig–ilm assemblage, with melt water contents around 4–6 wt %. At Santorini, the andesitic low-viscosity and water-rich residual liquids produced at these depths segregate from the parent basaltic mush and feed the shallow magma reservoirs, eventually erupting upon mixing with resident magma. Changes in prevailing oxygen fugacity may control the tholeiitic–calc-alkaline character of Santorini magmas, explaining the compositional and mineralogical differences observed between the recent Thyra and old eruptive products from Akrotiri.