Nematodes of the subfamily Nematodirinae are characteristic components of a Holarctic fauna. The topology of a generic-level phylogenetic hypothesis, patterns of diversity, and geographic distributions for respective nematode taxa in conjunction with data for host occurrence are consistent with primary distributions determined across Beringia for species of Murielus, Rauschia, Nematodirus, and Nematodirella. Ancestral hosts are represented by Lagomorpha, with evidence for a minimum of 1 host-switching-event and subsequent radiation in the Artiodactyla. Diversification may reflect vicariance of respective faunas along with episodic or cyclical range expansion and isolation across Beringia during the late Tertiary and Quaternary. Secondarily, species of Nematodirus attained a distribution in the Neotropical region with minimal diversification of an endemic fauna represented by Nematodirus molini among tayassuids, Nematodirus lamae among camelids and Nematodirus urichi in cervids during the Pleistocene. Nematodirines are a core component of an Arctic-Boreal fauna of zooparasitic nematodes (defined by latitude and altitude) adapted to transmission in extreme environments characterized by seasonally low temperatures and varying degrees of desiccation. The history and distribution of this fauna is examined in the context of biotic and abiotic determinants for geographic colonization and host switching with an exploration of predicted responses of complex host–parasite systems to ecological perturbation under a regime of global climate change.