In the present study, highly active nanocrystalline nickel oxide samples were prepared by using a simple, solvent-free, and cost-effective preparation method. Commercial nickel oxalate dihydrate powder was mixed with deionized water to form a soft paste which was sonicated till dryness and then, calcined in static air. The prepared nickel oxide samples were characterized by means of Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and N2 adsorption-desorption techniques. The surface basicity of the prepared oxide samples was measured by adsorption of CO2 molecules followed by desorption measurements using the thermogravimetry (TG) technique. The catalytic activity of the prepared nickel oxide samples towards the dehydrogenation of 2-butanol to methyl ethyl ketone (MEK) was studied at a temperature range of 225-325°C. The effects of calcination temperature, reaction temperature, and weight hourly space velocity WHSV on the catalytic activity were studied to determine the best calcination temperature and the optimum operating conditions. The sample calcined at 400°C showed the highest activity and the optimum operating conditions were found to be at the reaction temperature of 300°C and WHSV of 15 L h-1 g-1. The selectivity to MEK was higher than 85% for all the conducted experiments.