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Abstract This paper investigates the causes of the Late Cretaceous transition from “Sevier” to “Laramide” orogenesis and the spatial and temporal evolution of effective elastic thickness (EET) of the North American lithosphere. We use a Monte Carlo flexural model applied to 34 stratigraphic profiles in the Laramide province and five profiles from the Western Canadian Basin to estimate model parameters which produce flexural profiles that match observed sedimentary thicknesses. Sediment thicknesses come from basins from New Mexico to Canada of Cenomanian–Eocene age that are related to both Sevier and Laramide crustal loads. Flexural models reveal an east‐to‐west spatial decrease in EET in all time intervals analyzed. This spatial decrease in EET may have been associated with either bending stresses associated with the Sevier thrust belt, or increased proximity to attenuated continental crust at the paleocontinental margin. In the Laramide province (i.e., south of ~48°N) there was a coeval, regional decrease in EET between the Cenomanian–Santonian (~98–84 Ma) and the Campanian–Maastrichtian (~77–66 Ma), followed by a minor decrease between the Maastrichtian and Paleogene. However, there was no decrease in EET in the Western Canada Basin (north of ~48°N), which is consistent with a lack of Laramide‐style deformation or flat subduction. We conclude that the regional lithospheric weakening in the late Santonian–Campanian is best explained by hydration of the North American lithosphere thinned by bulldozing by a shallowly subducting Farallon plate. The weakening of the lithosphere facilitated Laramide contractional deformation by focusing end‐loading stresses associated with flat subduction. Laramide deformation in turn may have further reduced EET by weakening the upper crust. Finally, estimates of Campanian–Maastrichtian and Paleogene EET are comparable to current estimates indicating that the modern distribution of lithospheric strength was achieved by the Campanian in response to flat subduction.