Photocatalytic hydrogen evolution is a promising “green chemistry” route driven by sunlight for the direct water splitting into value-added hydrogen energy. Herein, with the object of exploring the effect of CuO loading on W18O49 photocatalytic activity, a 3D Urchin-like CuO modified W18O49 (CuO/W18O49) microspheres with different CuO loadings were synthesized via thermochemical precipitation combined with solvent-thermal method. The obtained CuO/W18O49 microspheres were analyzed by means of X-ray diffraction (XRD), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL), etc. The results infer that the urchin-like 3D morphology with a high surface area and abundant 1D nanowires promotes electron transfer, the introduction of CuO further increases the number of active sites, thereby ensuring fast interfacial charge transfer to improve photocatalytic performance. During photocatalytic H2 evolution from water splitting, 5 wt.% CuO/W18O49 shows the optimal performance, the H2 yield is almost 3.22 times that of the undoped counterparts. This work presents that oxygen-vacancy-rich heterojunction nanocomposites can be used as a new strategy to design materials with high photocatalytic activity.