Significance Water’s vibrational spectrum is dynamic: The OH oscillator frequency changes spontaneously within a diffuse envelope on an ultrafast timescale. Here, we explore the mechanics that drive this “spectral diffusion” at the molecular level by following the time-dependent frequency of single OH oscillators, each embedded in a cage of 20 deuterated water molecules, as a function of temperature. These cages are isolated in the gas phase and incorporate a single, isotopically labeled OH group that can occupy many spectroscopically distinct sites. The rates of spontaneous change in the OH frequency reflect the pathways for migration of the isotopic label among these sites, which occurs on a remarkably long (approximately millisecond) timescale at the onset of large-amplitude motion near 100 K.