The genus Cucurbita (Cucurbitaceae) includes five species that were domesticated independently in the Americas, giving rise to an immense diversity of squashes, pumpkins, and gourds. To gain an improved understanding of the evolution of Cucurbita and its domesticated taxa, we used four chloroplast loci to estimate the phylogeny of 23 taxa that represent the broad-level diversity within Cucurbita. Our results provide a strongly supported framework hypothesis for the phylogeny of the genus, robustly confirming the basal position of the C. digitata group of xerophytic perennials and the monophyly of a large group of mesophytic annuals that represent most of the known diversity in the genus, both wild and domesticated. The chloroplast evidence provides strong support for a novel grouping of the mesophytic annual C. ficifolia (known only from cultivation) with the xerophytic perennials C. foetidissima and C. pedatifolia. This study also provides the first DNA-based evidence in support of the isozyme-based hypothesis that C. pepo subsp. ovifera var. ovifera (represented by most ornamental gourds and several squashes) was domesticated from the wild taxon C. pepo subsp. ovifera var. ozarkana. This lends support to the hypothesis that var. ovifera was domesticated in the eastern United States and that this region served as one of about 10 independent centers of origin of human agriculture. Although the level of bootstrap support for this and certain other peripheral relationships in Cucurbita is low, definitive resolution of these issues is within reach, as next-generation sequencing should soon deliver entire organelle genome sequences from a comprehensive sampling of the genus.