Since the last glacial period, North America has experienced dramatic changes in regional climate, including the collapse of ice sheets and changes in precipitation. We use clumped isotope (∆47) thermometry and carbonate δ18O measurements of glacial and deglacial pedogenic carbonates from the Palouse Loess to provide constraints on hydroclimate changes in the Pacific Northwest. We also employ analysis of climate model simulations to help us further provide constraints on the hydroclimate changes in the Pacific Northwest. The coldest clumped isotope soil temperatures T((Formula presented.) 47) (13.5 ± 1.9°C to 17.1 ± 1.7°C) occurred ∼34,000–23,000 years ago. Using a soil-to-air temperature transfer function, we estimate Last Glacial Maximum (LGM) mean annual air temperatures of ∼−5.5°C and warmest average monthly temperatures (i.e., mean summer air temperatures) of ∼4.4°C. These data indicate a regional warming of 16.4 ± 2.6°C from the LGM to the modern temperatures of 10.9°C, which was about 2.5–3 times the global average. Proxy data provide locality constraints on the boundary of the cooler anticyclone induced by LGM ice sheets, and the warmer cyclone in the Eastern Pacific Ocean. Climate model analysis suggests regional amplification of temperature anomalies is due to the proximal location of the study area to the Laurentide Ice Sheet margin and the impact of the glacial anticyclone on the region, as well as local albedo. Isotope-enabled model experiments indicate variations in water δ18O largely reflect atmospheric circulation changes and enhanced rainout upstream that brings more depleted vapor to the region during the LGM.