The size distribution of lakes records the competition between precipitation delivery and evaporation. Lakes were abundant in the terminally draining basins of the western United States (USA) during both the colder-than-preindustrial latest Pleistocene glacial period (ca. 14–29 ka) and the warmer-than-preindustrial mid-Pliocene (ca. 2.9–3.3 Ma). To understand the hydroclimatic conditions that permitted lakes, we couple lake mass balance equations with a water and energy balance framework (sensu Budyko). Further, we compare paleo-lake area distributions to forward-modeled lake areas using climate model simulations of the Last Glacial Maximum (LGM, 19–26 ka) and mid-Pliocene. We conclude that both warmer- and colder-than-modern periods of the Pliocene–Pleistocene resulted in wetter-than-modern conditions in the terminally draining basins of the western USA through similar mechanisms. Specifically, the presence of lakes during the LGM reflects increased precipitation in addition to decreased evaporative demand. In the southern Great Basin, LGM lakes require large increases in precipitation across the region. During the mid-Pliocene, increased evaporative demand necessitated increased precipitation to maintain lakes. Further, the increase in precipitation and dominantly southwestern distribution of mid-Pliocene lake deposits is consistent with proposed mean “El Niño–like” conditions altering regional hydroclimate during this period. These observations suggest that during interglacial periods, the western USA resides within a local aridity maximum, and both long-term increases and decreases in global temperatures have been associated with wetter conditions across much of the western USA in the past.