Kimolos and Polyegos compound volcanoes, which belong to the Milos volcanic field in the South Aegean arc, Greece, mainly consist of late Pliocene volcanic units. Their history can be divided into two periods of activity separated by a long quiescence phase, as testified by thick epiclastic deposits. Basaltic to rhyolitic lavas and voluminous pyroclastic rocks were erupted during the first period, whereas rhyolitic pyroclastic deposits and perlitic lava domes characterize the second period of activity. During the general period of stasis, activity only occurred NE of Kimolos, where the Geronikolas tuff ring and lavas were emplaced. The rock composition belongs to the calc-alkaline and high-K calc-alkaline series. Olivine (Fo% = 63–68) is mainly found in the central Kimolos (Sklavos) basalts, and orthopyroxene (Mg# = 0.57–0.68) is stable in andesites at NE Kimolos (Geronikolas), whereas hornblende is abundant in some dacites (Vromolimni tuff). Clinopyroxene (Mg# = 0.62–0.85) and plagioclase (An% = 25–94) show large compositional ranges and complex zoning. Kimolos and Polyegos volcanics also show a large variability in trace-element contents and Sr and Nd isotope ratios (0.70456–0.70638 and 0.512484–0.512703, respectively), where the youngest rocks are more depleted in incompatible trace elements. Rhyolitic magmas are derived from the basalts by fractional crystallization and associated crustal assimilation and mixing processes, which occur at different crustal levels. The bimodal composition of the NE Kimolos (Vromolimni) tuff points to the presence of a zoned magma chamber refilled by mafic magmas. Magma source processes that imply different fluid to sediment-melt proportions of the subducted-mantle metasomatism components are responsible for the geochemical variability of mafic magmas. The genesis of the youngest magma is characterized by the lowest sediment input and the highest aqueous fluids and degrees of partial melting of the mantle source. Kimolos and Polyegos data have been interpreted in the context of the currently active South Aegean arc, where volcanic activity began in the western sector of the arc during the early Pliocene (4.7 Ma). Volcanism in the central sector of the arc began later. Partial melting of a mid-ocean-ridge basalt (MORB)–like asthenospheric mantle, metasomatized by subducted sediments and aqueous fluids, is thought to have produced all the South Aegean arc parental magmas. According to west-east isotopic trends, the amount of subducted sediments involved in the magma genesis decreases from west to east, together with a possible change in the composition of the subducted sediments. The lowest fluids to sediment-melts proportions are involved in the genesis of Santorini magmas, whereas the highest are involved in the magma genesis at Milos and Nisyros volcanic fields. The aqueous fluids should derive from subducted oceanic crust, at least in the central and eastern sectors of the arc. Most of the geochemical characteristics of the Santorini magmas are explained by higher partial melting degrees of the mantle source, probably triggered by the greater lithosphere extension, which induces adiabatic upwelling of the mantle. The higher lithosphere extension also causes Santorini magmas to reside at shallower levels, thus preventing amphibole crystallization and allowing a higher amount of mafic magmas to reach the surface. The Nisyros parental magmas are, on the contrary, generated by the least amounts of partial melting of the mantle. Partial melting degree of the mantle source seems to increase with time and passing from the external toward the central sectors of the arc.