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Northeast-striking tectonic provinces and boundaries were established during 1.8–1.6-Ga assembly of juvenile continental lithosphere in the southwestern United States. This continental grain repeatedly has influenced subsequent intracratonic tectonism and magmatism. After 200 m.y. of stability, cratonic lithosphere was affected by regional, ∼1.4-Ga, dominantly granitic magmatism and associated tectonism that reactivated older northeast-striking shear zones in the Proterozoic accreted terranes, but not the Archean lithosphere. In contrast, 1.1-Ga, dominantly mafic magmatism and rifting did not reactivate northeast-striking zones, but occurred along new north–south fracture zones (e.g., Rocky Mountain trend) that reflect cracking of Laurentian lithosphere at a high angle to the Grenville collision. By 500 Ma, rifting had thinned the crust and mantle in the western United States creating the north–south Cordilleran miogeocline. East of the Cordilleran hingeline, isopachs in Lower Paleozoic sedimentary rocks follow northeast-trending structures (Cheyenne belt, Transcontinental arch, and Yavapai–Mazatzal province boundary), suggesting that older boundaries influenced isostatic response of the craton during thermal subsidence of the margin. Ancestral Rockies and Laramide uplifts and basins did not strongly reactivate northeast-striking boundaries. However, Ancestral Rockies structures end at the Archean–Proterozoic boundary, and Laramide magmatism (Colorado mineral belt) and metallogenic provinces follow northeast-striking Proterozoic boundaries, both suggesting deep-seated lithospheric influences on tectonism. Present mantle structure and topography in the Rocky Mountain region continue to record an interaction between older crustal structures and younger mantle reorganization. Zones of partially molten mantle underlie northeast-striking Proterozoic boundaries (e.g., Snake River Plain, Saint George lineament, and Jemez lineament) and the north-striking Rio Grande rift, and are inferred to record replacement of lithosphere by asthenosphere preferentially along Archean–Proterozoic, Mojave–Yavapai, Yavapai–Mazatzal, and 1.1-Ga lithospheric anisotropies. Highest topography coincides with areas of low-velocity mantle, suggesting an importance of mantle buoyancy in the isostatic balance. Changes in topographic character across ancient crustal boundaries suggests a continued influence of crustal structures in differential uplift and denudation. Inheritance of the Proterozoic northeast grain involves two basic factors: (1) “volumetric” inheritance, in which density and fertility of lithospheric blocks of differing compositions influence isostatic and magmatic response to tectonism; and (2) “interface” inheritance, in which mechanical boundaries are zones of weakness and mass transport. “Volumetric” inheritance is suggested by the distinctive isotopic signatures of different provinces and by the observation that Archean lithosphere has been consistently less fertile for magmas than Proterozoic lithosphere, due to thicker, colder mantle, and compositional differences. We infer that distinct mantle lithospheres have been attached to their respective crustal provinces (at scales of 100 km) since accretion. “Interface” inheritance controls include mechanical reactivation of northeast-striking province boundaries and shear zones as magma conduits, zones of renewed shearing, and zones accommodating differential uplift.