Despite intensive morphological and molecular studies of Onagraceae, relationships within the family are not fully understood. One drawback of previous analyses is limited sampling within the large tribe Onagreae. In addition, the monophyly of two species-rich genera in Onagreae, Camissonia and Oenothera, has never been adequately tested. To understand relationships within Onagraceae, test the monophyly of these two genera, and ascertain the affinities of the newly discovered genus Megacorax, we conducted parsimony and maximum likelihood analyses with rbcL and ndhF sequence data for 24 taxa representing all 17 Onagraceae genera and two outgroup Lythraceae. Results strongly support a monophyletic Onagraceae, with Ludwigia as the basal lineage and a sister-taxon relationship between Megacorax and Lopezia. Gongylocarpus is supported as sister to Epilobieae plus the rest of Onagreae, although relationships within the latter clade have limited resolution. Thus, we advocate placement of Gongylocarpus in a monogeneric tribe, Gongylocarpeae. Most relationships within Onagreae are weakly resolved, suggesting a rapid diversification of this group in western North America. Neither Camissonia nor Oenothera appears to be monophyletic; however, increased taxon sampling is needed to clarify those relationships. Morphological characters generally agree with the molecular data, providing further support for relationships.