Sufficient data are available to interpret a general history of Cenozoic epeirogenic uplift and its influence on structure, salt dissolution, and topography in the Palo Duro basin. Much of the structural warping and deformation of Middle and Upper Permian rocks in the Palo Duro basin occurred during Cenozoic epeirogenic uplift. Cretaceous marine strata in the Texas and Oklahoma Panhandles and eastern New Mexico were uplifted 3,000-4,000 ft (914-1,219 m). The "Tubb Sand" (Permian) exhibits about 4,000 ft (1,219 m) of structural relief over the Amarillo uplift and Bravo dome.

Differential uplift of the margins of the basin caused draping, fracturing, and faulting, which increased the amounts and rates of erosion and salt dissolution coincident with fault-bounded structures. Structural control of topography around the southern high plains is indicated by the coincidence of the Caprock escarpment and structural highs in Permian rocks, as well as the coincidence of many stream segments and segments of the Caprock escarpment with subsurface fault trends.

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