Defect engineering offers a feasible avenue to ameliorate the photocatalytic activities of semiconductors, but the traditional preparation processes for introducing the defects would destroy the pristine morphology of the materials. Herein, a controllable defect engineering on CeO2 nanodots loaded Bi4TaO8Cl perovskite nanosheets was approached to synthesize well-defined CeO2/Bi4TaO8Cl (CE-BTC) heterojunction with stable oxygen vacancies (OVs) via a molten-salt-mediated strategy. Due to the coexistence of OVs and Ce4+/Ce3+ redox couple, the photo-Fenton degradation rate of ofloxacin by optimal CE-BTC heterojunction (0.09610 min−1) was 7.78 and 4.98 times higher than that by individual Bi4TaO8Cl and CeO2, respectively. Moreover, the CE-BTC also exhibited excellent degradation performance towards other antibiotics including norfloxacin, ciprofloxacin, tetracycline, and sulfamethoxazole, while maintaining good recyclability and stability. The high efficiency of CE-BTC was also attributed to its enhanced light-harvesting capability, low photogenerated carrier recombination, and minimal electron transfer resistance. Mechanism study indicated that ⋅OH and ⋅O2– were the dominant reactive species, whereas h+ also participated in the removal of ofloxacin with a lower contribution. This study demonstrated the enormous potential of CE-BTC heterojunction in the degradation and risk control of antibiotics, providing a promising strategy for designing highly dispersed heterojunction catalysts with surface defects.