The Grays River volcanics are part of the Coast Range basalt province and consist of ∼3500 m of tholeiitic basalt flows and volcaniclastic rocks that erupted in the Cascadia forearc from 42 to 37 Ma. Chemical and isotopic data, combined with migration of the location of magmatism through time, indicate that Grays River volcanics magmatism was related to subduction of a plume-influenced spreading ridge that produced a northward-migrating slab window. Involvement of a mantle plume source is indicated by ocean-island basalt (OIB)–like incompatible element enrichments and radiogenic Pb isotopic compositions (206Pb/204Pb > 19.3). These Pb isotope data are distinct from most Cascade arc rocks and from Cascadia sediment, but they overlap with compositions of other Coast Range basalts. A slab window setting accounts for the northward-younging age progression of the Grays River volcanics as well as geochemical traits, including low B/Be, that indicate the Grays River magmas ascended through the mantle wedge and subducting slab without acquiring an arc signature. Differentiation of Grays River magmas was dominated by clinopyroxene fractionation, which resulted in evolved compositions (Mg# = 59–32), low Sc contents, and Sr contents that increase with fractionation. Geochemical differences between the Grays River volcanics and other Cascadia forearc volcanic units that range from ca. 55 Ma (Crescent Basalts) to <3 Ma (Boring Lavas) were mainly caused by transient changes in tectonic setting (i.e., arrival of a mantle plume, ridge subduction) and do not record progressive chemical modification of the mantle wedge.