Despite the fact that fossil crocodylians have been recovered from the Panama Canal Zone starting with initial excavations in 1912, detailed studies have been lacking. Recent excavations of the canal have resulted in new discoveries of many vertebrate fossils, including the first known Miocene crocodylian skulls from Central America. These fossil skulls from the early–middle Miocene represent two new taxa with distinct morphology that is shared with extinct and extant caimans (Caimaninae). A cladistic analysis of 32 alligatorid and three outgroup taxa, scored for 75 characters, resulted in 1210 equally most parsimonious cladograms, all of which suggest that Culebrasuchus mesoamericanus, gen. et sp. nov., is the sister taxon to all previously known Caimaninae. Additionally, the analysis suggests that Centenariosuchus gilmorei, gen. et sp. nov., is the sister taxon to a caimanine clade that includes Purussaurus from the Miocene of South America. In fact, teeth very similar to those of Purussaurus have also been recovered from the Panama Canal. Given these South American affinities, we suggest that these early caimanines dispersed across saltwater. This is a potentially surprising result, because all extant alligatorids lack the salt glands that would have been necessary for the marine dispersal required to reach Central America during the Miocene. Unlike Miocene mammals that all have North American affinities, the Miocene crocodylians of Panama represent a ‘melting pot’ with taxa of disparate origins living together at the southern extreme of Central America.