The Paleogene fill of the northwestern Gulf of Mexico basin consists of eight genetic stratigraphic, sequences bounded by regional marine flooding surfaces. Calculation of sediment accumulation rates along dip profiles through four subbasins shows that regional changes in accumulation rate—and by inference, rate of sediment supply—of fivefold to tenfold repeatedly occurred over time spans of 1 to 3 m.y. Major sequences record episodes of high supply and accommodation-limited accumulation. Periods of declining and low supply were characterized by short-term over-accommodation and consequent transgressive flooding of the basin margin. Within sequences, depositional rates varied with position relative to the contemporaneous shelf margin, with type of depositional system, and between subbasins. Normal patterns of load-induced basin-margin subsidence and creation of accommodation space were modified by perturbation of the crustal stress regime.