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The Colville Igneous Complex is located within the Eocene Magmatic Belt of the North American Cordilleran interior. It straddles the US–Canadian border in northeast Washington and southern British Columbia. The complex consists of three intrusive and two extrusive phases, the first extrusive phase being contemporaneous with the latter two intrusive phases. As a consequence of sub-solidus re-equilibration in the plutonic rocks, this study concentrates on the two extrusive phases, the Sanpoil Volcanic Formation and the Klondike Mountain Formation. The Sanpoil Volcanic Formation consists of andesites, dacites and rare trachyandesites (SiO2 = 55–70 wt %) exhibiting a slight decrease in total alkalis (Na2O + K2O) with increasing silica. The Klondike Mountain Formation consists of basalts, basaltic andesites, andesites, dacites and rhyolites (SiO2 = 51–75 wt %) with total alkalis increasing with increasing silica. The calc-alkaline affinity of the rocks of the Colville Igneous Complex, coupled with the presence of a 'subduction signature' of enriched large ion lithophile elements (LILE) and depleted high field strength elements (HFSE), has traditionally been attributed to petrogenesis in a subduction-related magmatic arc, the 'Challis Arc'. New trace and rare earth element and isotopic data (87Sr/86Sri, ϵNdi, δ18O), however, suggest that this explanation is no longer tenable. We propose that the magmas of the Sanpoil Volcanic Formation were generated by mid-crustal partial melting of a mid-Proterozoic source and that the Klondike Mountain Formation was formed by varying degrees of mixing between two distinct late-Proterozoic lower-crustal sourced magmas and a mantle-derived magma. In all cases, the subduction or calc-alkaline signature was inherited from the Proterozoic crustal sources. The only magmas that can confidently be attributed to a mantle source are the basalts of the Klondike Mountain Formation, which show no decoupling of the LILE and HFSE, i.e. no subduction signature, precluding the presence of a subduction slab beneath this part of the North American Cordillera during the Eocene. We propose the alternative model: that the Colville Igneous Complex formed as a result of decompression melting of crust and mantle during post-Laramide orogenic collapse of an overthickened crust.