The history and connections of the flora of North America have been studied and summarized in biogeographic regionalization. However, some studies show contrasting delineations of the North American provinces that could be better determined using quantitative methods. We aimed to find spatial patterns of a set of plants in the United States by conducting endemicity analysis (EA) on different scales. We first built a dataset with 215,772 specimen point records of 731 species from 235 genera and 76 families of angiosperms and two genera of gymnosperms using digitized specimen data from iDigBio. We then performed EA at four different scales to identify the areas of endemism (AoEs). We obtained 31 AoEs with different cell sizes by selecting each AoE under the grid size that yielded the highest number of high-scoring species. The study region split into three floristic centers, the Northwestern and Eastern, both supporting the Boreal subkingdom of Takhtajan, and the Madrean, supporting the namesake subkingdom of the Holarctic Kingdom. The Madrean Subkingdom showed two significant centers of accumulation of nested or partially overlapping AoEs: the SW and SC consensus areas. In these parts of the study area, many genera/clades, among those in the dataset, showed a geographic split into western and eastern clades. Most significant in endemism AoEs, the Sonora–Mojave arid center, Chihuahuan Desert, the California Floristic province, Gulf Coastal Plain, and southern Appalachians, harbor basally branching taxa of several genera, subfamilies, and even families, based on the observations of some species, which allowed identification of the AoEs. Northwestern AoEs showed connections to East Asia across the Bering Land Bridge, Madrean AoEs – had mostly southern, especially along the backbone of the Andies and amphitropical, connections, while eastern AoEs– showed tmperate connections mostly across the Atlantic and, in Gulf Coastal Plain, to the tropical New World, or broader tropical floras.