Zn-Co-S ball-in-ball hollow sphere (BHS) was successfully prepared by solvothermal sulfurization method. An efficient strategy to synthesize Zn-Co-S BHS consisted of multilevel structures by controlling the ionic exchange reaction was applied to obtain great performance electrode material. Carbon nanotubes (CNTs) as a conductive agent were uniformly introduced with Zn-Co-S BHS to form Zn-Co-S BHS/CNTs and expedited the considerable electrocatalytic behavior toward glucose electro-oxidation in alkaline medium. In this study, characterization with scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) was used for investigating the morphological and physical/chemical properties and further evaluating the feasibility of Zn-Co-S BHS/CNTs in non-enzymatic glucose sensing. Electrochemical methods (cyclic voltammetry (CV) and chronoamperometry (CA)) were performed to investigate the glucose sensing performance of Zn-Co-S BHS/CNTs. The synergistic effect of Faradaic redox couple species of Zn-Co-S BHS and unique conductive network of CNTs exhibited excellent electrochemical catalytic ability towards the glucose electro-oxidation, which revealed linear range from 5 to 100 μM with high sensitivity of 2734.4 μA mM−1 cm−2, excellent detection limit of 2.98 μM, and great selectivity in the presence of dopamine, uric acid, ascorbic acid, and fructose. Thus, Zn-Co-S BHS/CNTs would be expected to be a promising material for non-enzymatic glucose sensing.