Designing ultrathin two-dimensional (2D) defective materials and metal-free doped materials as photocatalysts both have received enormous attentions in the field of environmental remediation due to their great potential for removing colorless contaminants. However, whether the synergism of defects and metal-free doping exists and the corresponding oxidative mechanism is unclear, which retard further developments of high performance catalysts. Here, a novel oxygen vacancy (OV)-rich ultrathin sulfur-doped BiOBr nanosheet (BB-xS) was synthesized through a facile one-step solvothermal method. Under visible light irradiation, the optimal BB-5S sample exhibited 98% degradation efficiency of 4-chlorophenol (4-CP) within 120 min, which was 4.9 and 18.0 times greater than that of pristine ultrathin BiOBr and oxygen vacancy-poor sulfur-doped BiOBr, respectively. Also, this excellent photoactivity could extend to other colorless organic contaminants, such as bisphenol analogues and sulfonamides, verifying the universal applicability of BB-xS. Based on experimental results and density functional theory (DFT) calculations, it was manifested that a sub-band was generated via the synergistic effect of oxygen vacancies and sulfur doping, and it greatly enhanced the visible-light absorption capability and suppressed the photoinduced charge recombination, which would be beneficial to improve the photocatalytic activity. Additionally, the corresponding photocatalytic degradation pathway of 4-CP was also proposed. This work can provide a new protocol for the design and construction of highly active photocatalysts toward environmental remediation.