Though rapid phenotypic evolution has been observed in many invasive plant species, less is known about the associated genetic mechanisms. Some hypotheses invoke the evolution of trade-offs in resource allocation to explain phenotypic differences between the native and invaded ranges of a species. Alternately, invasive species may benefit from a generalist strategy and perform well in many environments. Identification of the molecular changes associated with successful invasions can offer clues regarding the mechanistic basis of such hypotheses, even in non-model organisms. To complement studies of phenotypic variation, we investigate gene expression during drought response that might underlie variation in drought tolerance between native and introduced populations of diffuse knapweed (Centaurea diffusa), and possibly contribute to invasion success. Using species-specific microarrays and tissue sampled under drought and control conditions at three time points, we identified genes whose expression either varied constitutively or responded to drought stress differently between ranges. Further, we functionally investigate these genes. Based on these data, invasive populations have constitutively higher levels of expression relating to energy production and lower levels of signal transduction expression relative to native populations. Under drought conditions, invasive populations may maintain energy production and react less strongly to drought than native populations, which may allow them to maintain fitness across moderate environmental variation. This supports the expectation of invasive populations consisting of generalist genotypes capable of fitness homeostasis, which may have facilitated the successful invasion of many environments in North America