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The Pliocene to Quaternary volcanic arc of the Central Andes formed on 70–74 km thick continental crust. Physical interaction between mafic and acid magmas for this arc are therefore difficult to recognize due to the differentiation of mantle-derived magma during ascent through the thickened crust and a corresponding lack of erupted primitive lavas. However, a rare concentration of less evolved rocks is located marginal to the partially molten Altiplano-Puna Magma Body (APMB) in the Altiplano-Puna Volcanic Complex of northern Chile, between 21°10′S and 22°50′S. To unravel the relationship between this less evolved magmatism and the APMB, we present major and trace element data, and Sr and Nd isotope ratios of fourteen volcanoes. Whole-rock compositional and Sr and Nd isotope data reveal a large degree for compositional heterogeneity, e.g., SiO 2 = 53.2 to 63.2 wt%, MgO = 1.74 to 6.08 wt%, Cr = 2 to 382 ppm, Sr = 304 to 885 ppm, 87Sr/86Sr = 0.7055 to 0.7088, and 143Nd/144Nd = 0.5122 to 0.5125. The combined dataset points to magma spatial compositional changes resulting from magma mixing, fractional crystallization and crustal assimilation. The least evolved products erupted along the periphery of the APMB and are likely equivalent to the replenishing magmas that thermally sustain the large APMB system. We suggest that the mafic to intermediate eruptives we have investigated reflect mafic melt injections that underplate the APMB and escape along the side of the large felsic body to avoid significant compositional modifications during ascent, which helps to assess the evolution of the APMB through space and time. Unlabelled Image • Olivine and two-pyroxene phyric rocks are concentrated marginal to the large felsic Altiplano-Puna Magma Body (APMB). • The compositional variability is explained by the involvement of magma mixing/assimilation of the APMB, coupled assimilation and fractional crystallization (AFC), or selective assimilation of the most fusible portions of the continental crust. • Crustal contamination involving APMB melts decreases as APMB vertical mush thickness decreases for the investigated eruptives. • The APMB remains thermally active due to steady replenishment of mafic melt from depth and may have slightly reduced its molten extent at least since Pliocene times. [ABSTRACT FROM AUTHOR]