The areal and temporal distribution and the chemical and isotopic characteristics of Cenozoic volcanic rocks from the Oregon Plateau reflect the changing tectonic conditions affecting this area over the last 20 m.y. Following subduction zone related calc-alkaline volcanism, flood basalt eruptions occurred in the time interval 18–14 Ma. This primarily basaltic volcanism is interpreted to be the result of a major shift in spreading orientation of the Juan de Fuca ridge that resulted in changes in the geometry of subduction against the Pacific Northwest. The compositions of the mid-Miocene flood basalts show signs of extensive crystal fractionation, in some cases accompanied by crustal contamination. Roughly 11 m.y. ago, basalt eruptions showed an increasing tendency toward smaller volumes and less evolved compositions. This implies that as extension in the Oregon Plateau proceeded, the crust became less of an impediment to the passage of relatively unfractionated mantle melts. Initial Sr, Nd, and Pb isotopic compositions of all the basalts show more correlation with the geographic position of eruption than with the composition of the lava. Primary control over the isotope systematics appears to be due to changes in the age and chemical characteristics of the crust and mantle throughout this area. These observations suggest that an area of some 130,000 km2 of crust and basalt depleted subcontinental mantle has been added to northwestern North America over the last 20 m.y. The intensity of basalt volcanism as manifest in the Columbia River Group and in the Oregon Plateau does not appear to reflect the presence of a “hot spot” beneath the area. Both the areal and temporal distribution of the lavas and their geochemical characteristics are more easily reconciled with the suggestion that this crustal section grew by “back arc” spreading in a manner analogous to the formation of the marginal basins of the western Pacific. This spreading initiated along the western border of the Archean Wyoming craton with the location of mantle ascent, melt production, and extraction controlled by the changing geometry of subduction, the existence of a zone of lithospheric weakness, and the presence of a thick, low-density, subcontinental mantle “keel” existing beneath the Archean craton in this area.