Volcanic rocks of the Jurassic Iskut River Formation (IRF) in northwestern British Columbia (Canada) host several volcanogenic massive sulfide (VMS) deposits, including the exceptionally high-grade Eskay Creek Ag–Au–Cu–Pb–Zn deposit. The IRF comprises voluminous pillow basalt (>90%), minor rhyolite, and sedimentary rock of late Early to early Middle Jurassic age, filling a series of sub-basins along a 300 by 50 km north-trending belt. Two geochemically distinct types of tholeiitic basalts interfinger; both resemble back-arc basin basalts formed from the melting of asthenospheric and sub-arc mantle sources. Group 2 basalts are more enriched in light rare-earth elements, Ba, K, Sr, Th, and U, and have lower positive εNd values than group 1 basalts (+3.2 to +6.3 versus +6.9 to +8.4, respectively). The compositional differences between group 1 and group 2 basalts are interpreted to result from crustal contamination in group 2. Group 1 basalts are most common in the southern part of the IRF belt where they are closely associated with the Eskay Creek, Bonanza, and Hidden Creek (Anyox) VMS deposits. Group 2 basalts are most abundant in the northern half of the belt and are not associated with exploited mineral deposits. The lack of crustal contamination in group 1 basalts indicates that they formed from rapidly ascending magma in an advanced rift setting and were associated with high heat flow that drove hydrothermal circulation. Group 1 and group 2 basalts are reliably discriminated by Ta/Th <2.5 in the former and >;2.5 in the latter. This geochemical criteria can therefore be used as an exploration tool to identify VMS permissive sub-basins and (or) stratigraphy in the IRF.