Continental-scale drainages host the world’s largest rivers and offshore sediment accumulations, many of which contain significant petroleum reserves. Rate of sediment supply in these settings may be a signal of external controls (e.g., tectonics) on landscape evolution, yet deciphering these controls remains a major challenge in interpreting the ancient stratigraphic record. Integration of new and published detrital zircon U-Pb ages from the United States Rocky Mountain region and Gulf of Mexico (GOM) sedimentary basin demonstrates profound changes in the U.S. continental drainage divide that controlled the rate of sediment delivery to the northern GOM during Paleocene–Eocene time. Sedimentation rate increased dramatically during deposition of the lower Wilcox Group, reaching approximately three times the Cenozoic average, accompanied by pronounced shoreline regression and delivery of a large volume of sand to the basin floor. We hypothesize that this increase in sediment delivery to the GOM resulted from drainage capture of a significant portion of the Sevier-Laramide structural province (∼900,000 km2) that included the headwaters of the California and Idaho Rivers. Capture of the California River drainage may have occurred in the vicinity of the Hanna Basin of eastern Wyoming that previously emptied northward into a shallow seaway, but was subsequently diverted southward to the Rockdale delta, which accumulated within the Houston embayment during the time of deposition of the lower Wilcox Group. Detrital zircon U-Pb ages from Wilcox samples within the Rockdale delta show a remarkable similarity with contemporaneous Laramide synorogenic units, including enrichment in detritus derived from the Cordilleran arc and basement terranes of western North America relative to older and younger units in the Houston embayment. A subsequent order of magnitude decline in sedimentation rate to the GOM can be partly attributed to well-documented drainage closure (∼800,000 km2) that accompanied lake formation in interior Laramide basins (ca. 53–51.8 Ma). Our results demonstrate that tectonically induced drainage migration in the high-relief segments of continental-scale drainages can have a pronounced effect on the rate of sediment transfer to continental margins.