We use in situ scanning probe microscopy (SPM) to investigate the high temperature oxidation of Ni-based single crystal alloys at the micro-/nanoscale. SiO2 micro-pillar arrays were pre-fabricated on the alloy surface as markers before the oxidation experiment. The SPM measurement of the oxidized surface in the vicinity of SiO2 micro-pillars was conducted real time at temperatures from 300 °C to 800 °C. The full-field evolution of oxide film thickness is quantitatively characterized by using the height of SiO2 micro-pillars as reference. The results reveal the non-uniform oxide growth featuring the nucleation and coalescence of oxide islands on the alloy surface. The outward diffusion of Ni and Co is responsible for the formation and coalescence of first-stage single-grain oxide islands. The second-stage of oxidation involves the formation and coalescence of poly-grain oxide islands.