NiO with novel flower-like morphology was prepared by using a two-step, template-and surfactant-free, environmentally friendly method. Flower-like NiO was composed of many irregular nanosheets that were assembled together by weak interactions. The as-prepared materials were characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, transmission electron microscopy with selected area electron diffraction patterns, N2 sorption, temperature-programmed reduction with CO, X-ray photoelectron spectroscopy (XPS), and in situ Fourier transform infrared (FT-IR) for CO adsorption. The catalytic behaviors for CO oxidation were studied by using a fixed bed microreactor. Compared to NiO nanoparticles, we found the flower-like NiO possessed a larger surface area, bimodal pore size distribution, higher reducibility, and superior catalytic activity for CO oxidation. The XPS and CO in situ FT-IR results showed that its catalytic property was morphology dependent. The flower-like morphology provided more coordinate unsaturated Ni atoms, more oxygen vacancies, and more defect sites, which made the flower-like NiO have a strong interaction with CO and more active sites for catalytic reactions. Further studies showed that a mild condition for thermodecomposition of the precursor was necessary to preserve the flower-like morphology because of the large discrepancy of the crystalline cell structures between the β-Ni(OH) 2 precursor and product of NiO.