The Southwest United States is prone to severe and persistent drought1, but the influence of anthropogenic forcing on current and future precipitation remains uncertain2-7. To improve our understanding of the drivers of Southwest drought, we quantified precipitation and temperature changes in the southern Rockies and combined these with a multi-model ensemble of climate simulations for the mid-Holocene, a past interval when the region experienced exceptional and persistent drought. Reconstructed mid-Holocene warming in the Rockies is consistent with existing proxy reconstructions. In most models, this warming only occurs in simulations with prescribed mid-Holocene vegetation, including a “greening” of the Sahara, supporting the hypothesis that expanded vegetation was critical for producing warming consistent with proxy data15. In response to this hemispheric warming, a distinct pattern of higher temperatures resembling the negative phase of the Pacific Decadal Oscillation emerges in the models, increasing the magnitude of wintertime precipitation declines across the western US, in better agreement with proxy reconstructions. A similar forced response could be excited by anthropogenic forcings, enhancing future drought across the Southwest US. However, reductions in winter precipitation associated with the development of this pattern of North Pacific warming are underestimated in simulations of both the mid-Holocene and the instrumental period, suggesting that current projections may underestimate the magnitude and the risk of persistent human-made drought in the future.