A coordinated, multidisciplinary study was conducted to elucidate the mechanism for oxygen enhanced crack growth in Inconel 718 at high temperatures. Sustained-load tests were conducted in high-purity argon and oxygen, at 873 to 973 K, to characterize the kinetics of crack growth. The reactivity of the alloy, Nb, NbC and Ni3Nb with oxygen was determined by x-ray photoelectron spectroscopy (XPS). Crack growth experiments, in oxygen at 973 K, were interrupted and the specimens were charged with hydrogen and fractured in UHV to determine the state of oxidation of various elements, particularly ahead of the crack tip. The existence of a damage zone ahead of the crack tip had been demonstrated previously by reloading interrupted specimens of comparable alloys in argon at lower temperatures and stress intensity levels. A mechanism for oxygen enhanced crack growth in Inconel 718, based on the formation of a brittle niobium oxide film ahead of the crack tip from the oxidation of grain boundary Ni3Nb and Nb-rich carbides, is proposed and discussed.