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The Central Andes of South America are one of the highest and broadest mountain ranges on earth and have a profound influence on climate in the Southern Hemisphere. Yet, the timing of Andean uplift and its subsequent impact on atmospheric circulation is not well known. Here we use fossil soils from along an 800-km transect (19-25 degrees S) in the Atacama Desert of northern Chile to identify the initiation of extreme aridity along the west coast of South America and infer a minimum age for the development of the Central Andean rain-shadow. Paleosols record the onset of extreme aridity at the boundary between the middle and late Miocene (12-10 Ma). Lower Miocene (24-20 Ma) soils are chemically weathered and contain soil carbonate, indicative of a vegetated landscape and semi-arid climate. In contrast, gypsum dominates massive (2-5 m thick) upper middle Miocene soils that formed on a hyperarid landscape devoid of vegetation. The development of extreme hyperaridity is linked to the formation of the Central Andean rain-shadow through the divergence of oxygen isotope values. Oxygen isotope values of lower Miocene soil carbonates in the Atacama Desert (-5.0 +/- 1.1 parts per thousand VPDB) and Central Andes (-7.8 +/- 1 parts per thousand) are similar, indicating no or a limited rain-shadow. By 15 Mya, however, delta O-18 values of soil carbonate differ by similar to 8 parts per thousand, with values of soil carbonate in Altiplano paleosols getting lower due to uplift while soil carbonate values in the Atacama Desert get higher due to aridity. Therefore, by 15 Mya there is clear evidence for a rain-shadow from the Central Andes. By the latest middle Miocene (ca. 12-10 Ma), paleosols in the Altiplano decreased to -11.8 +/- 1.0 parts per thousand while soils in the Atacama Desert increase to +1.5 +/- 4.5 parts per thousand. This almost 14 parts per thousand divergence in the delta O-18 values of soil carbonate for soils only similar to 250 km apart is evidence of a strong Central Andes rain-shadow effect in place during the late middle Miocene (12-10 Ma). (C) 2018 Elsevier B.V. All rights reserved.