A new classification for the freshwater crabs of the Americas, the superfamily Pseudothelphusoidea¸ is presented based on a multigene phylogeny complemented by morphological analyses. We propose that the superfamily Pseudothelphusoidea be composed of two families, the Epiloboceridae and the Pseudothelphusidae, with the subsequent reorganization of the latter into eight subfamilies, of which five (Hypolobocerinae, Kingsleyinae, Potamocarcininae, Pseudothelphusinae, Strengerianinae) represent previously recognized tribes. We erect three new subfamilies: Guinotiinae, Ptychophallinae and Raddausinae, to reflect relationships that have become clear with the new analyses. The new classification scheme has a high level of congruence with the geographical distribution of species and genera. A divergence time estimate suggests that the Pseudothelphusoidea originated in the late Cretaceous around 68 Mya. Subsequent divergence events can be correlated with emergent landmasses throughout the range of the superfamily. There is high concordance among several elements of our proposal: (1) the main morphological types of male gonopods correspond to well defined clades obtained with molecular analyses; (2) the geographic distribution of the subfamilies has a structured pattern; and (3) the estimated times of divergence of each group can be associated to the geological history of each region. The combination of these elements results in a robust new classification scheme.