Why is species diversity so unevenly distributed across different regions on Earth? Regional differences in biodiversity may stem from differences in rates of speciation and dispersal and colonization times, but these hypotheses have rarely been tested simultaneously at a global scale. Our study reveals the macroevolutionary routes that have generated hotspots of mammal and bird biodiversity by analyzing the tempo and mode of diversification and dispersal within major biogeographic realms. Hotspots in tropical realms had higher rates of speciation, whereas those in temperate realms received more immigrant species from their surrounding regions. We also found that hotspots had higher spatial complexity and energy availability, providing a link between the environment and macroevolutionary history. Our study highlights how assessing differences in macroevolutionary history can help to explain why biodiversity varies so much worldwide.