We present a new model for the genesis of low-δ18O rhyolites of the Yellowstone caldera based on analyses of zircons and individual quartz phenocrysts. Low-δ18O rhyolites were erupted soon after the massive caldera-forming Lava Creek Tuff eruption (602 ka, ∼1000 km3) and contain xenocrysts of quartz and zircon inherited from precaldera rhyolites. These zircons are isotopically zoned and out of equilibrium with their host low-δ18O melts and quartz. Diffusion modeling predicts that magmatic disequilibria of oxygen isotopes persists for as much as tens of thousands of years following nearly total remelting of the hydrothermally altered igneous roots of the depressed cauldron, in which the alteration-resistant quartz and zircon initially retained their δ18O values. These results link melting to caldera collapse, rule out rapid or catastrophic magma–meteoric water interaction, and indicate wholesale melting rather than assimilation or partial melting.