Combined heavy mineral analysis and detrital zircon geochronology have enabled us to track detritus supplied by the ancestral river systems draining the North American continent into the deep subsurface of the Gulf of Mexico, in both the coastal plain and the offshore deep water areas. During deposition of the Paleocene–Eocene Wilcox Group, sandstones in the western part of the area are interpreted as the products of the Rosita system derived via paleo-Rio Grande material, with a large component of sediment shed from the Western Cordillera. By contrast, samples from wells further east have high proportions of zircons derived from the Yavapai-Mazatzal Province and are attributed to the Rockdale system with sediment fed predominantly by the paleo-Colorado or paleo-Colorado-Brazos. There is evidence that sediment from the Rosita system occasionally extended into the central Gulf of Mexico, and, likewise, data indicate that the Rockdale system sporadically supplied sediment to the western part of the basin. During the Late Eocene of the central Gulf of Mexico (Yegua Formation) there was a distinct shift in provenance. The earlier Yegua sandstones have a large Grenville zircon component and are most likely to have had a paleo-Mississippi origin, whereas the later Yegua sandstones are dominated by zircons of Western Cordilleran origin, similar to Wilcox sandstones fed by the Rosita system via the paleo-Rio Grande. The switch from paleo-Mississippi to paleo-Rio Grande sourcing implies there was a major reorganisation of drainage patterns during the Late Eocene. Miocene sandstones in the deepwater Gulf of Mexico were principally sourced from the paleo-Mississippi, although the paleo-Red River is inferred to have contributed to the more westerly-located wells.