Constructing novel heterojunctions has become an effective strategy to improve the performance of photoelectrochemical (PEC) biosensors, but most of the glucose-sensing photoelectrodes involve enzyme modification and disordered or semi-closed surface topography which restricts the working environment and sensing performance. Herein, the dense and burr-like CuO nanospikes (CuONSs) are grown on all over the whole surfaces of the relatively-sparse and ordered Si nanowires (SiNWs) by a combination of magnetron sputtering and hydrothermal growth. The optimized SiNWs-CuONSs heterojunction with a core–shell structure achieves the enzyme-free PEC detection of glucose with a sensitivity of 2324.09 μA mM−1 cm−2 in the concentration range of 0–1.0 mM and a detection limit of 0.74 μM (Signal/Noise = 3). The excellent sensing performance is ascribed to that (1) the SiNWs with a large specific surface area acting as host have open-style surface topography, ensuring the analyte flowability; (2) the CuONSs with a desired glucose-catalytic activity are hierarchical, providing a great number of active sites; and (3) the SiNWs-CuONSs heterojunction has a satisfactory optical absorption and a high efficiency of the photogenerated-hole transfer. This work demonstrates that the enzyme-free and highly-sensitive glucose detection can be realized by morphology-controllable heterojunction, and provides an alternative route to noninvasive sensing.