Covalent organic frameworks (COFs) have attracted significant attention in photocatalytic water purification due to their structural designability and sufficiently negative conduction band edges. However, the limited oxidation capacity of single COFs and the low utilization rate of photogenerated carriers result in suboptimal catalytic activity. To address these challenges, we propose a two-level regulation strategy that involves ligand engineering and the introduction of a piezoelectric field to enhance the photocatalytic performance of COF-based photocatalysts. In this study, we combined the piezoelectric material Bi2WO6 with COFs modified with different ligands to design a series of Bi2WO6/R-COFs (R=H, F, CH3O) heterojunctions. Modifying COFs with –OCH3 functional group tuned the local electron distribution, thereby remarkably improving photogenerated electrons transfer rate constant. Besides, the incorporation of Bi2WO6 generated a piezoelectric field under ultrasound, which provides a strong driving force for photocatalytic. Meanwhile, the construction of the heterojunctions offered multi-channel for the generation of reactive oxygen species. As a result, the photocatalytic degradation rate of Bi2WO6/CH3O-COFs reached 93.5 % toward sulfamethoxazole within 48 min under ultrasound-coupled light irradiation, which is nearly three times higher than Bi2WO6/H-COFs. Furthermore, Bi2WO6/CH3O-COFs demonstrated superior degradation performance for other pollutants, including p-chlorophenol, bisphenol A, tetracycline, and phenol, with degradation efficiencies of 99.0 %, 98.4 %, 93.5 % and 88.1 %, respectively. This work proposes a two-level modulation strategy that significantly enhances the antibiotic degradation performance of COF-based catalysts, offering a new perspective for the design of photocatalysts for environmental remediation.