The European conquest of the New World produced major socio-environmental reorganization in the Americas, but for many specific regions and ecosystems, we still do not understand how these changes occurred within a broader temporal framework. In this paper, we reconstruct the long-term environmental and vegetation changes experienced by high-altitude wetlands of the southcentral Andes over the last two millennia. Pollen and charcoal analyses of a 5.5-m-long core recovered from the semi-arid puna of northern Chile indicate that while climatic drivers influenced vegetation turnaround, human land use and management strategies significantly affected long-term changes. Our results indicate that the puna vegetation mostly dominated by grasslands and some peatland taxa stabilized during the late Holocene, xerophytic shrubs expanded during extremely dry events, and peatland vegetation persisted in relation to landscape-scale management strategies by Andean pastoralist societies. Environmental changes produced during the post-conquest period included the introduction of exotic taxa, such as clovers, associated with the translocation of exotic herding animals (sheep, cattle, and donkeys) and a deterioration in the management of highland wetlands.