The enemy release hypothesis (ERH) of plant invasion asserts that natural enemies limit populations of invasive plants more strongly in native ranges than in non-native ranges. Despite considerable empirical attention, few studies have directly tested this idea, especially with respect to generalist herbivores. This knowledge gap is important because escaping the effects of generalists is a critical aspect of the ERH that may help explain successful plant invasions. Here, we used consumer exclosures and seed addition experiments to contrast the effects of granivorous rodents (an important guild of generalists) on the establishment of cheatgrass (Bromus tectorum) in western Asia, where cheatgrass is native, vs. the Great Basin Desert, USA, where cheatgrass is exotic and highly invasive. Consistent with the ERH, rodent foraging reduced cheatgrass establishment by nearly 60% in western Asia but had no effect in the Great Basin. This main result corresponded with a region-specific foraging pattern: rodents in the Great Basin but not western Asia generally avoided seeds from cheatgrass relative to seeds from native competitors. Our results suggest that enemy release from the effects of an important guild of generalists may contribute to the explosive success of cheatgrass in the Great Basin. These findings corroborate classic theory on enemy release and expand our understanding of how generalists can influence the trajectory of exotic plant invasions.