Nanocrystalline Inconel 625 alloy, with a uniform distribution of grains, was synthesized using cryogenic mechanical milling. Microstructures of the powder, cryomilled for different times, were investigated using transmission electron microscopy (TEM), scanning electron microscopy, and x-ray diffraction. The results indicated that both the average powder particle size and average grain size approached constant values as cryomilling time increased to 8 h. The TEM observations indicated that grains in the cryomilled powder were deformed into elongated grains with a high density of deformation faults and then fractured via cyclic impact loading in random directions. The fractured fragments from the elongated coarse grains formed nanoscale grains. The occurrence of the elongated grains, from development to disappearance during intermediate stages of milling, suggested that repeated strain fatigue and fracture, caused by the cyclic impact loading in random directions, and cold welding were responsible for the formation of a nanocrystalline structure. A high density of mechanical nanotwins on {111} planes was observed in as-cryomilled Inconel 625 powders cryomilled, as well as in Inconel 625 powder milled at room temperature, Ni20Cr powder milled at room temperature, and cryomilled pure Al.