The occurrence of isotopically uniform quartz (δ18O = 12.5‰ ± 0.5‰) and feldspar (10.9‰ ± 0.7‰) throughout different rock types indicates that much of a 6-km-thick section of the mid-crustal Selkirk allochthon underwent internally buffered 18O/16O homogenization during Paleocene melting and decompression as it moved up the Monashee thrust ramp. Areas of uniform δ18O are those with the most leucogranite or those subjected to severe anatexis. Only locally, in the most impermeable (or refractory) zones did 18O exchange among the rocks, leucogranite melts, and aqueous fluids fail to go to completion (i.e., in the deepest parts of the section, in a marble-rich zone, around some thick amphibolites, and in most garnets). Evidence for 18O/16O heterogeneity in the protoliths of these rocks is observed in stratigraphically correlative lower-grade units elsewhere in British Columbia, as well as in garnets that coexist with isotopically homogeneous quartz. In our model, 18O/16O homogenization accompanied muscovite dehydration and partial melting of pelites with only minor influx of external H2O, followed by release of magmatic H2O from these melts (triggering further melting of adjacent feldspathic assemblages) as they were uplifted 20 km during thrusting just prior to onset of detachment faulting. Locally, low δ18O in feldspar (down to −3.8) and profound quartz-feldspar 18O/16O disequilibrium were imprinted at shallow levels during meteoric-hydrothermal alteration associated with Eocene detachment faulting.