By electrodeposition and galvanic replacement reaction, we developed a facile, time-saving, cost-effective, and environmentally friendly, two-step synthesis route to obtain a controllable cobalt oxide/Au hierarchically nanostructured electrode for glucose sensing. The nanomaterials were characterized by transmission electron microscopy, scanning electron microscopy, Raman spectroscopy, energy-dispersive spectrometry, and X-ray photoelectron spectroscopy, meanwhile, the sensing performance was investigated by cyclic voltammetry and amperometric response. The results revealed that this novel electrode exhibited excellent electrocatalytic performance toward glucose oxidation, with a wide double-linear range from 0.2 μM to 20 mM and a low detection limit of 0.1 μM based on a signal-to-noise ratio of 3, which was mainly attributed to the ability of loading a small amount of Au with good electron conductivity on the surface of cobalt oxide nanosheets with large active surface area and synergistic electrocatalytic activity of Au and cobalt oxide toward glucose electrooxidation. This facile, sensitive, and selective glucose sensor is also proven to be suitable for the detection of glucose in human serum.