Mesoamerica is famous for its complex biota assembled from diverse sources. The recent discovery of a highly distinct freshwater catfish, Lacantunia enigmatica (Lacantuniidae), in Chiapas, México, added an unresolved taxon to this biogeographic puzzle. Morphology has not resolved the relationships of Lacantunia among the >3000 species of Siluriformes. We added Lacantunia to an expanding phylogenetic study of family-level taxa of living catfishes using >3.6 kilobases of nuclear DNA. We find that Lacantunia is derived from within a multi–family clade of African freshwater catfishes. Without living or fossil intermediates marking a wider lacantuniid distribution, this is an extraordinary case of biogeographic disjunction. Continental clades distributed in the New and Old World tropics are often explained by vicariance of Gondwanan ancestors of deep Mesozoic age. However, our fossil-calibrated, relaxed-clock molecular analyses estimate lacantuniid divergence between 75 to 94 mya, after separation of Africa and South America. During Late Cretaceous and early Tertiary, warm conditions and North Atlantic and Beringian land bridges provided migration routes for numerous warm-adapted taxa between the Old World and North America. In mid-Eocene, freshening of warm surface waters of the Arctic and adjacent oceans may have facilitated the intercontinental dispersion of non-marine organisms. These northern pathways are novel predictive hypotheses for explaining disjunct distributions of tropical freshwater fishes such as the relictually endemic Lacantunia and its African sister clade.