The mechanisms driving late Holocene drought cycles in the western United States are not well known due to the general scarcity of long-term, high-resolution, absolutely dateable proxies for precipitation in continental interiors. Here we show that late Holocene precipitation variability in the southwestern United States has been caused by changes in the Pacific Ocean. We present a stalagmite-based, annually resolved moisture record that indicates large shifts from pluvial to drought conditions alternating with periods of dampened, near-average precipitation over the last 3000 years. Significant spectral peaks at decadal-scale (~20--50, 70--80 year) frequencies likely correspond to modern frequencies of the Pacific Decadal Oscillation or a low-frequency component of the El Ni¿o-Southern Oscillation, and are dominant during episodes of large precipitation shifts. Overall pluvial conditions punctuated by severe droughts may have challenged the adaptive capacities of emerging agrarian communities of ancestral Americans.