We describe Tupelocetus palmeri, a new genus and species of archaeocete whale, based on a single specimen from the Cross Member of the middle Eocene Tupelo Bay Formation (Bartonian). The holotype consists of a partial cranium with complete petrosals, posterior processes of tympanics, the posterior ends of the nasals, a part of the right orbit, and what are interpreted as the right and left P2s. The incomplete skull was collected from the Martin Marietta Cross Quarry (Berkeley County, South Carolina), which has also furnished the holotype of Carolinacetus gingerichi. The new species differs from all other protocetids in having a deep cavity on the occiput, as well as having the following combination of features: large nasal processes of frontals, single-cusped P2, and premaxilla terminates at level of P2 or P3. A phylogenetic analysis places T. palmeri in a large polytomy along the cetacean stem, more closely related to crown Cetacea than Maiacetus, Artiocetus, and Rodhocetus, but more basal than Georgiacetus, Babiacetus, and Eocetus. Another member of this polytomy is Natchitochia jonesi, and although specimens of Natchitochia and T. palmeri do not share any elements, what is preserved suggests that they are similar in size and among the largest of all protocetids. Although we are unable to differentiate these two species, we outline future data that could resolve this question.