Hyphessobrycon is one of the most species rich and widely distributed genera in the family Characidae, with more than 160 species ranging from Veracruz, Mexico to Mar Chiquita Lagoon in Buenos Aires, Argentina. The majority of Hyphessobrycon diversity shows a cis-Andean distribution; only nine species are trans-Andean including H. compressus (Meek 1908). It is well established that Hyphessobrycon is not monophyletic but it has been suggested that natural groups can be identified within the larger Hyphessobrycon species group. In this study, we tested the monophyly of trans-Andean species of Hyphessobrycon and investigated the placement of H. compressus. We inferred the first phylogenomic hypothesis of trans-Andean Hyphessobrycon that includes nearly complete taxonomic sampling (eight of nine valid species) using ultraconserved elements (UCEs). We analyzed 75% (1682 UCEs), 90% (1258 UCEs), and 95% (838 UCEs) complete data matrices, and inferred phylogenomic hypotheses under concatenation and coalescent approaches. In all cases, we recovered the monophyly of trans-Andean Hyphessobrycon inclusive of H. compressus, strong support for three species groups, and evidence of cryptic diversity within the widespread H. compressus and H. condotensis. We used our phylogenomic hypothesis to investigate the biogeographic history of Hyphessobrycon in Middle America. Our ancestral range estimation analysis suggests a single event of cis- to trans-Andean colonization followed by stepwise colonization from the Pacific slope of northwestern South America (Chocó block) to northern Middle America (Maya block). Our work supports the recognition of the trans-Andean species as Hyphessobrycon sensu stricto and provides an evolutionary template to examine morphological characters that will allow us to better understand the diversity of Hyphessobrycon in Middle America.