Three-dimensional (3D) photocatalytic heterostructures have attracted intense interest, due to their interlayer synergy and high quantum yield. Bismuth oxyiodide (BiOI) is considered as a useful semiconductor material due to its narrow bandgap, good visible-light absorption and tendency to form anisotropic heterostructures. Herein, we propose a facile design strategy for structure-controlled nano-flower-like BiOI/MoS microspheres with uniform size and enhanced capacity to photodegrade tetracycline (TC) and methyl orange (MO). These 3D BiOI/MoS microspheres were outstanding catalysts of visible-light-driven contaminant degradation, as shown by their ability to degrade TC and MO three times and four times faster, respectively, than pure BiOI. This excellent photocatalytic performance of 3D BiOI/MoS microspheres is attributable to synergistic effects resulting from their unique defect-rich structure, specifically the loading of MoS onto the surface of defect-rich BiOI suppressing recombination of photogenerated electron–hole pairs. Moreover, the abundant active edge-sites and unique physicochemical properties of MoS nanosheets enables them to inhibit photogenerated electron–hole recombination. In this study, a novel route for synthesis of structure-controlled nano-flower-like BiOI/MoS microspheres was developed, which will increase the application of these useful materials for addressing environmental pollution. An important direction in future research will be to develop large-scale, controllable synthesis and interfacial microstructural control of these heterostructured photocatalysts.