Central to debate about the age, origin, and evolution of Grand Canyon (southwestern United States) is the history of the Colorado River and its precursors. Reversal of dextral slip along the San Andreas fault system since the early Pliocene restores southern California to the downstream end of the Colorado River. If the Colorado River flowed to the Pacific Ocean prior to 6 Ma, then its sand would have the distinctive detrital-zircon age distributions of upper Paleozoic and Mesozoic strata of the Colorado Plateau, which contain 30%–46% 300–1100 Ma zircon originally transported from orogenic belts of southeastern Laurentia. In contrast, age distributions of 6662 detrital zircons from 167 Upper Cretaceous–Pliocene sandstone samples from southern California average 44%–88% Cretaceous, with only 0.4%–1.3% 300–1100 Ma grains, most of which can be attributed to local recycling from older deposits. No individual Upper Cretaceous to Pliocene sandstone sample from southern California contains >3% 300–1100 Ma zircon. Although Paleogene headwaters of southern California rivers extended into the eastern Mojave Desert, Sonoran Desert, and Mogollon Highlands, our results indicate that these headwaters did not extend as far as the Colorado Plateau. This conclusion conflicts with the hypothesis of a Paleogene southwest-flowing Arizona River, but supports late Miocene–Pliocene drainage reorganization and integration of the Colorado River coincident with development of the Salton Trough and Gulf of California.