Aim Our aims were: (1) to use recently published phylogenies of six widely distributed clades of highland-type fishes in a comparative analysis that investigates relationships among North American highlands; (2) to construct a map of relevant (pre-historic) river geography; and (3) to apply ecological paradigms to interpret patterns of highland-fish cladogenesis. Our principal questions were: (1) does highland endemism correspond to pre-historic river drainages; and (2) do patterns of speciation conform to any relevant paradigm?Location Twenty-two North American highlands, east to west from Appalachia to the Basin and Range, north to south from the Canadian Shield to the Mesa Central.Methods We used three-item analysis to find shared highland-area relationships, and we used dated phylogenies and geological literature to construct a map of relevant, pre-historic river drainages. We applied the taxon-cycle concept to interpret results.Results Three-item analysis identified 375 most-parsimonious trees with a retention index of 80.4%. An intersection tree reconstructed from shared three-area statements had a completeness index of 80.3%. Nodes on the tree identified seven major branches of one to eight highland areas each that were congruent with late Miocene river drainage patterns. Sister-area relationships within nodes were congruent with Plio-Pleistocene events. Older taxa have restricted distributions and some younger members of each clade are broadly distributed, consistent with predictions of the taxon cycle.Main conclusions Progenitors of highland endemics were widespread across an aggraded, alluvial landscape by the early Miocene. Middle Miocene drainage rearrangements facilitated further range expansion. Accelerated erosion in the middle Miocene, caused by tectonic uplift and climate change, created highland-type (sediment-starved) habitats. Parallel colonization and adaptation to these habitats and geographical isolation in the late Miocene and early Pliocene led to speciation of highland endemics. Plio-Pleistocene drainage rearrangements allowed populations of tolerant (derivative) taxa to expand again and colonize highland areas, including emerging ones.