Significance This study provides conservation assessments for 600 US native plants that are wild relatives of important agricultural crops. We found that more than one-half of the species may be endangered in their natural habitats, and that the great majority require further conservation action, both ex situ (in gene banks and botanical gardens) and in situ (in protected areas). Diversity hotspots across the nation represent focal regions for further collecting for ex situ conservation as well as for enhanced habitat protection. Wider collaborations, as well as greater awareness, access to, and information about these resources are needed to bolster their conservation and use.