The shrub honey mesquite (Prosopis glandulosa var. glandulosa Torr.) readily encroaches into rangelands in the southwestern United States that vary in annual rainfall by almost a factor of 5 (200 to 1 000 mm). This occurs partly because mesquite seedlings grow rapidly and become uncoupled from competition with established herbaceous vegetation. Species that occupy such a wide precipitation gradient frequently include plants that differ genetically in seedling growth rate. Whether atmospheric carbon dioxide (CO₂) enrichment affects seedling biomass uniformly across mesquite genotypes or magnifies the expression of genetic variation in seedling growth remains unresolved. We measured the effects of CO₂ enrichment on growth of seedlings derived from 14 adult plants (open-pollinated families), 7 plants each from rangelands located near extremes of the rainfall gradient occupied by the shrub (arid southeastern New Mexico vs. mesic central Texas). Growth was measured over days 10 to 30 following emergence on well-watered seedlings in glasshouses at ambient and elevated CO₂ concentrations (391 and 706 μmol·mol⁻¹, respectively). Proportional responses of biomass (day 30) to CO₂ enrichment varied from 1.03 to 1.74 among families. CO₂ enrichment did not consistently favor the largest or fastest-growing families at ambient CO₂. Rather, proportional responses of biomass to elevated CO₂ were highly correlated across families with the stimulation of relative growth rate (RGR) at elevated CO₂. Biomass at ambient CO₂ was 19% greater, on average, in families from mesic rangeland than from arid rangeland, but families from extremes of the precipitation gradient did not diverge by seedling size or response to CO₂. Selection for greater RGR could augment the mean growth response of mesquite seedlings to CO₂. Even in the absence of selection, CO₂ enrichment could increase mesquite establishment by enhancing seedling growth and thereby exacerbate the management challenge of minimizing woody encroachment.