Plant macrofossils from 33 rodent middens sampled at three sites between 2910 and 3150 m elevation in the main canyon of the Río Salado, northern Chile, yield a unique record of vegetation and climate over the past 22,000 cal yr BP. Presence of low-elevation Prepuna taxa throughout the record suggests that mean annual temperature never cooled by more than 5°C and may have been near-modern at 16,270 cal yr BP. Displacements in the lower limits of Andean steppe and Puna taxa indicate that mean annual rainfall was twice modern at 17,520–16,270 cal yr BP. This pluvial event coincides with infilling of paleolake Tauca on the Bolivian Altiplano, increased ENSO activity inferred from a marine core near Lima, abrupt deglaciation in southern Chile, and Heinrich Event 1. Moderate to large increases in precipitation also occurred at 11,770–9550 (Central Atacama Pluvial Event), 7330–6720, 3490–2320 and at 800 cal yr BP. Desiccation occurred at 14,180, 8910–8640, and 4865 cal yr BP. Compared to other midden sites in the region, early Holocene desiccation seems to have happened progressively earlier farther south. Emerging trends from the cumulative midden record in the central Atacama agree at millennial timescales with improved paleolake chronologies for the Bolivian Altiplano, implying common forcing through changes in equatorial Pacific sea-surface temperature gradients.