Subduction zone magmatism is a major control of volcanism, the generation of modern continental crust and the formation of economically important porphyry Cu–(Mo–Au) deposits. Reading the magmatic record of individual arc segments and constraining the rates of magmatic changes are critical in order to fully understand and quantify the processes that drive magma evolution in subduction settings during arc growth. This study focuses on the San Francisco Batholith and the Rio Blanco-Los Bronces porphyry deposit cluster in central Chile, which provides an igneous rock record over ~13.5 Myr of arc evolution. We use whole-rock geochemistry, zircon geochronology and Hf isotope geochemistry to track changes in the crustal magmatic system of this arc segment during crustal thickening and porphyry Cu deposit formation. By combining the analytical dataset with Monte Carlo fractional crystallisation and assimilation fractional crystallisation modelling, we test a model for significant crustal involvement during magma evolution. Systematic and continuous increases in Dy/Yb, La/Yb, V/Sc and Sr/Y in the magmas over time indicate a transition in the main fractionation assemblage from plagioclase-dominated to amphibole-dominated that reflects deeper crystallisation and/or a higher meltwater content. Concomitant decreases in εHf and Th/La as well as increasing Ba/Th are best explained by assimilation of progressively deeper crustal lithologies from low (Chilenia) to high Ba/Th (Cuyania) basement terranes. Our study highlights that an increasingly hydrous magma and a deepening locus of crustal magma differentiation and assimilation, driven by crustal thickening contemporaneous with increased tectonic convergence and ingression of the aseismic Juan Fernandez ridge, can account for all investigated aspects of the multi-Myr magmatic evolution leading up to the formation of the Rio Blanco-Los Bronces porphyry Cu deposits. Our findings corroborate the importance of high-pressure differentiation of hydrous magma for the formation of Andean-style porphyry deposits. Once magmas favourable for porphyry Cu mineralisation were generated in the lower crust, multiple episodes of efficient magma migration into the upper crust fed several, discrete, shallow magmatic-hydrothermal systems over ~3.5 Myr to form the world’s largest known Cu resource at Rio Blanco-Los Bronces.