North America is a large continent with extensive climatic, geological, soil, and biological diversity. That biota is under threat from habitat destruction and climate change, making a quantitative assessment of biodiversity of critical importance. Rapid digitization of plant specimen records and accumulation of DNA sequence data enable a much‐needed broad synthesis of species occurrences with phylogenetic data. Here we attempted the first such synthesis of a flora from such a large and diverse part of the world: all seed plants for the North American continent (here defined to include Canada, United States, and Mexico) with a focus on examining phylogenetic diversity and endemism. We collected digitized plant specimen records and chose a coarse grain for analysis, recognizing that this grain is currently necessary for reasonable completeness per sampling unit. We found that raw richness and endemism patterns largely support previous hypotheses of biodiversity hotspots. Application of phylogenetic metrics and a randomization test revealed novel results, including significant phylogenetic clustering across the continent, a striking east‐west geographic difference in the distribution of branch lengths, and the discovery of centers of neo‐ and paleo‐endemism in Mexico, the southwestern USA, and the southeastern USA. Finally, our examination of phylogenetic beta‐diversity provides a new approach to comparing centers of endemism. We discuss the empirical challenges of working at the continental scale, and the need for more sampling across large parts of the continent, for both DNA data for terminal taxa and spatial data for poorly understood regions, to confirm and extend these results.