In this work, ZnO–CuO composite porous spheres with core–shell structure were successfully synthesized through a controllable simple top-down route to take advantage of the excellent features of ZnO and CuO. The crystal structure and morphology of the as-prepared products were characterized, and a possible growth mechanism was proposed. The obtained sample with a core surrounded by a porous shell has a large surface area. As CuO can well catalyze glucose in alkaline solution, together with the good electron transfer property of ZnO and the hetero-junction formed between them, non-enzymatic glucose sensors based on ZnO–CuO composite porous spheres show good performance with a wide linear range of 0.02–4.86 mM, a high sensitivity of 1,217.4 μA cm−2 mM−1, and a low detection limit of 1.677 μM, indicating a good detection behavior of glucose.