The Andean continental arc is built upon the thickest crust on Earth, whose eruption products reflect varying degrees of crustal assimilation. In order to robustly model magma evolution and assimilation at subduction zones such as the Andes, the compositions of parental magmas feeding crustal magma reservoirs need to be defined. Here we present new olivine and clinopyroxene oxygen isotope data from rare mafic volcanic rocks erupted at the margins of the giant Altiplano-Puna Magma Body (APMB) of the Altiplano-Puna Volcanic Complex, Central Andes. Existing olivine and pyroxene δ18O values for the Central Andes are highly variable and potentially not representative of sub-arc parental compositions. However, new olivine (n = 6) and clinopyroxene (n = 12) δ18O values of six Central Andean volcanoes presented here display a narrow range, with averages at 6.0‰ ± 0.2 (2σ S.D.) and 6.7‰ ± 0.3 (2σ S.D.), consistent with a common history for the investigated minerals. These data allow us to estimate the δ18O values of sub-arc, parental melts to ca. 7.0‰ ± 0.2 (2σ S.D.). Parental melts feeding the APMB and associated volcanic centres are postulated to form in the felsic continental crust following assimilation of up to 28% high-δ18O basement rocks by mantle-derived magmas.