Nickel oxide (NiO) nanocrystals epitaxially grown on (001) strontium titanate (SrTiO3) single crystal substrates were characterized to investigate interface morphology and chemistry. Aberration corrected high angle annular dark field scanning transmission electron microscopy reveals the interface between the NiO nanocrystals and the underlying SrTiO3 substrate to be rough, irregular, and have a lower average atomic number than the substrate or the nanocrystal. Energy dispersive x-ray spectroscopy and electron energy loss spectroscopy confirm both chemical disorder and a shift of the energy of the Ti L2,3 peaks. Analysis of the O K edge profiles in conjunction with this shift, implies the presence of oxygen vacancies at the interface.This sheds light into the origin of the previously postulated minority carriers’ model to explain resistive switching in NiO [J. Sullaphen, K. Bogle, X. Cheng, J. M. Gregg, and N. Valanoor, Appl. Phys. Lett. 100, 203115 (2012)].