By modifying habitats and creating bridges and barriers between landmasses, climate change and tectonic events are believed to have important consequences for diversification of terrestrial organisms. Such consequences should be most evident in phylogenetic histories of groups that are ancient, widespread, and diverse. The squirrel family (Sciuridae) is one of very few mammalian families endemic to Eurasia, Africa, and North and South America and is ideal for examining these issues. Through phylogenetic and molecular-clock analyses, we infer that arrival and diversification of squirrels in Africa, on Sunda Shelf islands, across Beringea, and across the Panamanian isthmus coincide in timing and location with multiple well-documented sea-level, tectonic, and paleontological events. These precise correspondences point to an important role for global change in the diversification of a major group of mammals.