The Arequipa-Antofalla Basement, a Proterozoic crustal block exposed along the central Andean margin, provides a key to interpreting the pre-Andean history of South America. New U/Pb geochronology and whole-rock Pb and Nd isotope geochemistry from the Arequipa-Antofalla Basement refine the tectonic history and delineate three distinct crustal domains that decrease in age from north to south. The northern domain of southern Peru and western Bolivia contains juvenile Paleoproterozoic 2.02-1.79 Ga intrusions that were metamorphosed at 1.82-1.79 Ga. The Mesoproterozoic central domain in northernmost Chile contains a significant Mesoproterozoic juvenile component that incorporates Paleoproterozoic crust from the northern domain. Rock units from both the northern and central domains were metamorphosed between 1.20 and 0.94 Ga, with coeval magmatism occurring only in the central domain. The southern domain in northern Chile and northwestern Argentina comprises Ordovician rocks, derived from a mix of juvenile material and older crust. Similar Ordovician magmatism (476-440 Ma) also occurred in the northern and central domains followed by metamorphism at ca. 440 Ma. Based on this refined geologic and tectonic characterization of the Arequipa-Antofalla Basement and comparison with that of Amazonia, we conclude that: (1) the isolated exposures of the Arequipa-Antofalla Basement comprise a single basement block with multiple domains, (2) the Arequipa-Antofalla Basement was not derived from Amazonia, and (3) the Arequipa-Antofalla Basement accreted onto Amazonia during the 1.0 Ga Sunsás Orogeny.