Continental sedimentation reflects a complex interplay of tectonics and climate. A 2000-km transect from coastal California to the western Great Plains documents a major increase in sedimentation (ca. 16–6 Ma) coeval with deposition of the hemipelagic Monterey Formation along the California coast. Basin and Range-style regional extension following elongation of the Pacific–North American transform boundary at ca. 17.5 Ma provided fault-bounded basins for accommodation space, but sedimentation also occurred on unextended erosional surfaces of the Great Plains and Colorado Plateau. Two global climate transitions bracket this sedimentary interval. The middle Miocene transition (ca. 17–12 Ma) records the global change from equatorial to meridional circulation caused by: (1) closing of the eastern Tethys Seaway (ca. 18 Ma); (2) opening of the Arctic–North Atlantic connection (ca. 17.5 Ma); (3) growth of the East Antarctic Ice Sheet (ca. 14 Ma); and (4) closing of the Indonesian Seaway (ca. 12 Ma). Upwelling of cold waters along the California coast, abetted by domination of La Niña phases of El Niño–Southern Oscillation (ENSO), progressively aridified the Southwest as reflected in sedimentary and biologic records. The second climate transition occurred as opening of the Gulf of California (ca. 6 Ma) intensified the North American monsoon, resulting in integration of drainages, incision of uplifts, and exhumation of basin fills. The Miocene ended with the driest climate of the Tertiary (both regional and global) accompanied by conversion of savanna to steppe or scrub desert, spread of C4 grasses, and the greatest mammal extinction of the Neogene.