In light of suggestions that the Cascadia subduction margin may pose a significant seismic hazard for the highly populated Pacific Northwest region of the United States, the U.S. Geological Survey (USGS), the Research Center for Marine Geosciences (GEOMAR), and university collaborators collected and interpreted a 530-km-long wide-angle onshore-offshore seismic transect across the subduction zone and volcanic arc to study the major structures that contribute to seismogenic deformation. We observed (1) an increase in the dip of the Juan de Fuca slab from 2°–7° to 12° where it encounters a 20-km-thick block of the Siletz terrane or other accreted oceanic crust, (2) a distinct transition from Siletz crust into Cascade arc crust that coincides with the Mount St. Helens seismic zone, supporting the idea that the mafic Siletz block focuses seismic deformation at its edges, and (3) a crustal root (35–45 km deep) beneath the Cascade Range, with thinner crust (30–35 km) east of the volcanic arc beneath the Columbia Plateau flood basalt province. From the measured crustal structure and subduction geometry, we identify two zones that may concentrate future seismic activity: (1) a broad (because of the shallow dip), possibly locked part of the interplate contact that extends from ∼25 km depth beneath the coastline to perhaps as far west as the deformation front ∼120 km offshore and (2) a crustal zone at the eastern boundary between the Siletz terrane and the Cascade Range.