Within southeast British Columbia, mid-Cretaceous granitoid batholiths are exposed in the Omineca Belt, a north–south-trending metamorphic and plutonic orogenic belt. The Bugaboo, Horsethief Creek, and Fry Creek batholiths are post-kinematic with respect to regional metamorphism that affected their host rocks, and are composed of hornblende and biotite granodiorites and granites in all three batholiths, and two-mica granites in Fry Creek. The biotite granites are weakly peraluminous, have initial εSr ranging from + 36 to + 56 and initial εNd ranging from −4.8 to −7.5, and overlap the range of Nd–Sr isotopic compositions for Precambrian basement gneisses and Proterozoic metasediments found in southeast British Columbia. The initial 206Pb/204Pb versus 208Pb/204Pb and 207Pb/204Pb for these granitoids lie in bands between model lower and upper crustal Pb isotopic compositions above the Northern Hemisphere Reference Line for oceanic basalts. These granitoids have high Nb and Rb and low Ba abundances relative to granites found in volcanic arcs. The two-mica granites are strongly peraluminous and have εSr ranging from + 170 to + 470, εNd ranging from −10 to−21, and more radiogenic initial Pb-isotope ratios than the biotite granites. The two-mica granites have trace element compositions similar to those of granites found in within-plate and collisional tectonic settings.We favor a model for crustal anatexis of Precambrian basement gneisses and Proterozoic metapelites to produce the mid-Cretaceous biotite granites and two-mica granites, respectively. Crustal anatexis was likely in response to crustal thickening that occurred during the Mesozoic in southeast British Columbia as exotic terranes collided with and were accreted to the western edge of the North American continent.