A nanocomposite of ZnV2O6 with hierarchical flower-like structure hybridized with reduced graphene oxide (rGO) was fabricated using a facile hydrothermal approach. The structure, morphology, optical and electronic properties were explored using comprehensive analytical techniques. The results revealed that the rGO sheets were decorated with the in situ-formed ZnV2O6 nanoparticles yielding a well-combined composite structure. The photocatalytic activity of as-prepared ZnV2O6/rGO hybrids is 2.48 times larger than that of pristine ZnV2O6 for the degradation of Rhodamine B (RhB). In parallel to the experimental results, the basic mechanisms of interfacial interaction, charge transfer/separation and subsequently their influence on the photocatalytic activity were theoretically studied by first-principles calculations. The photocatalytic enhancement is attributed to efficient interfacial electron transfer from ZnV2O6 to rGO, leading to a prolonged lifetime of photoinduced charge carriers. We anticipate that these results will lead to new insights in the judicious design of graphene-based semiconductor photocatalysts.