The scale-up of the gas-liquid mixing process is a challenging task. Some of these challenges are associated with the fluid’s non-Newtonian behavior resulting in oxygen depletion zones upon scale-up. Coaxial mixers have shown a uniform energy dissipation rate throughout the tank and a superior mass transfer rate. However, no investigation has been conducted on the scale-up of the aerated coaxial mixers to the best of our knowledge. Therefore, a scale-up study of an aerated coaxial mixer comprised of a single central impeller and an anchor filled with a non-Newtonian fluid was conducted using the constant mass transfer (k_La) method. In this study, to maintain the large-scale mixer’s k_La the same as its small-scale counterpart, the gas hold-up profile, energy dissipation rate profile, power consumption, and mixing hydrodynamics were investigated. The effects of the impeller type, impeller speed, pumping direction, and aeration rate were explored on the reliability of the scale-up technique through electrical resistance tomography, simplified dynamic pressure method, and computational fluid dynamics. It was found that at the same central impeller tip speed and anchor impeller rotational speed, the flow regime attained by the large-scale mixer was the same as its small-scale counterpart. Furthermore, it was found that the anchor impeller speed should be kept constant in both small-scale and large-scale mixing systems. This was due to the fact that in the large-scale mixer, the central impeller pumping capacity decreased by increasing the anchor impeller speed. Finally, it was observed that keeping both the aeration rate per working fluid volume and the specific power consumption constant between the two scales was the optimum approach to preserve the mass transfer coefficient constant upon scaling-up of the coaxial mixer.