This study assessed variations in leaf intrinsic water use efficiency (iWUE) and delta 15N values among Encelia, a genus of drought-deciduous shrubs distributed across arid regions of southwestern North America between 1972 and 1980 when climates were cooler than today. We hypothesized that geographical variations in climate would significantly influence iWUE, a response to water-related climate constraints, and delta 15N values, a proxy for the balance between N2 fixation and denitrification. Leaf samples were collected from six species of Encelia across 78 sites representing the genus range. The delta 15N and delta 13C values of these samples were measured and analyzed to identify drivers of spatial variability. Significant variations among iWUE and delta 15N values were observed as a function of climate, along a spring-summer precipitation gradient. Precipitation and vapor pressure deficit (VPD) were significant drivers of variations in iWUE values, with iWUE increasing with VPD and/or decreasing precipitation, as would be predicted based on water-related constraints on leaf gas exchange. Climate values were significant drivers of variations in delta 15N values, with lower delta 15N values occurring in cooler temperature, spring-growing plants (northern latitudes) than in warmer summer-growing plants (southern latitudes). Encelia leaf iWUE and delta 15N observations suggest few, if any, species-specific differences; but more likely that there is high plasticity in these values driven by variations in climate.