Solar-driven elimination of refractory contaminants is an ideal route to tackle the environmental issues. Nevertheless, the photocatalytic performance of photocatalysts is heavily restrained due to the insufficient accessible reactive sites and fast electrons/holes reunion. Herein, a novel metal–organic framework-based S-scheme heterostructure of MIL-101(Fe)/Bi2WO6 was synthesized by a simple solvothermal approach. The optimized MIL-101(Fe)/Bi2WO6 (MIL/BWO-2) affords the highest photo-activities under visible light, which are 13.7, 6.7 folds greater for Cr(VI) reduction, and 0.8, 10.5 folds higher for tetracycline hydrochloride oxidation compared with individual Bi2WO6 and MIL-101(Fe), respectively. The preeminent catalytic capability lies in two aspects: 1) the introduction of MIL-101(Fe) substantially enlarges the surface area of the composites, offering ample reaction sites and fostering pollutant adsorption and mass transportation; 2) the novel S-scheme photo-carrier transport mechanism assisted by oxygen vacancies favors spatial segregation and transport of photoinduced electrons/holes with superior redox capacity. Reactive species identification experiments verify that O2– and e– dominantly contribute to Cr(VI) reduction, while O2–, h+ and OH account for tetracycline hydrochloride destruction. Furthermore, the tetracycline photo-decomposition pathway, eco-toxicity evaluation, and photocatalytic mechanism were investigated comprehensively. This research paves the way for building high-performance MOFs-based S-scheme heterojunctions toward photocatalytic water purification.