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Mexico is considered an exceptional biogeographic area with a varied endemic flora, however spatial phylogenetic measures of biodiversity have not yet been estimated to understand how its flora assembled to form the current vegetation. Patterns of species richness, endemism, phylogenetic diversity, phylogenetic endemism and centers of neo- and paleo-endemism were determined to examine differences and congruence among these measures, and their implications for conservation. Of 24360 vascular plant species 10235 (42%) are endemic. Areas of endemism and phylogenetic endemism were associated with dry forests in zones of topographic complexity in mountain systems, in deserts, and in isolated xeric vegetation. Every single locality where seasonally tropical dry forests have been reported in Mexico was identified as an area of endemism. Significant phylogenetic diversity was the most restricted and occurred in the Trans-Mexican Volcanic Belt and in the Sierra de Chiapas. Notably, the highest degree of phylogenetic clustering comprising neo-, paleo-, and super-endemism was identified in southernmost Mexico. Most vascular plant lineages diverged in the Miocene (5-20mya) when arid environments expanded across the world. The location of Mexico between two very large landmasses and the fact that more than fifty percent of its surface is arid favored the establishment of tropical lineages adapted to extreme seasonality and aridity. These lineages were able to migrate from both North and South America across Central America presumably during the Miocene and to diversify, illustrating the signature of the flora of Mexico of areas of endemism with a mixture of neo- and paleo-endemism.