Much of North America’s freshwater biodiversity is derived from Palearctic lineages. Isopods of the Holarctic family Asellidae are among the most widespread and diverse freshwater crustaceans, but Nearctic species are poorly studied. We examined the evolutionary history of the family, utilizing Sanger sequencing of mitochondrial and nuclear DNA, and both Maximum-Likelihood and Bayesian Inference. The genera Calasellus and Salmasellus from the western United States are shown to be basally derived, suggesting they have only distant affinity to other Nearctic taxa and represent relictual lineages taht likely diverged in the Jurassic. Remaining Nearctic asellids formed a monophyletic group sister to the Lake Baikal endemic genus Baikalasellus, which diverged during the Early Cretaceous. Our results show a close connection between Nearctic and eastern Palearctic asellids, with an Early Cretaceous divergence consistent with limited connections between Asia and North America. We propose that asellids used a Beringian route to colonize the Nearctic from west to east, in contrast to Europe-to-North America routes hypothesized for other freshwater crustaceans. Many of the genera we analyzed were non-monophyletic; taxonomic revision may shed further light on the route and timing of asellid diversification in the Nearctic and on the processes by which freshwater taxa colonized this realm.