Giant earthquakes have repeatedly ruptured the Cascadia subduction zone, and similar earthquakes will likely also occur there in the near future. We employ a 3-D time-dependent thermomechanical model that incorporates an up-to-date description of the slab geometry to study the Cascadia subduction thrust. Results show a distinct band of 3-D slab dehydration that extends from Vancouver Island to the Seattle Basin and further southward to the Klamath Mountains in northern California, where episodic tremors cluster. This distribution appears to include a region of increased dehydration in in northern Cascadia. The phenomenon of heterogeneous megathrust seismicity associated with oblique subduction suggests that the presence of fluid-rich interfaces generated by slab dehydration favors megathrust seismogenesis in the northern part of this zone. The thin, relatively weakly metamorphosed Explorer, JF, and Gorda plates are associated with an anomalous lack of thrust earthquakes, and metamorphism that occurs at temperatures of 500-700°C near the Mohorovičić discontinuity may represent a key factor in explaining the presence of the associated ETS, which requires a young oceanic plate to subduct at a small dip angle, as is the case in Cascadia and southwestern Japan. The stratified intra-slab dehydration structure suggests that the metamorphosed plate environment is more complex than had previously been believed, despite the existence of channeling vein networks. Slab amphibolization and eclogitization near the continental Moho depth is thus inferred to account for the resultant overpressurization at the interface, facilitating the generation of ETS and the occurrence of small to medium thrust earthquakes beneath Cascadia.