The photochemical transformation of fluoroquinolones (FQs) represents a crucial environmental phenomenon eliciting growing concern. Nevertheless, the impact and mechanisms of ubiquitously coexisting copper ions, i.e., Cu(II), remain elusive. Here, the role of Cu(II) in the photochemical transformation of FQs was systematically investigated via experimental characterizations and theoretical simulations. Cu(II) markedly inhibited the photolysis of levofloxacin (LEV), a representative FQs model, from 0.0078 to 0.0040 min-1 after a 100-min irradiation under simulated sunlight with the molar ratio of Cu(II): LEV at 1:1. The micro-level mechanisms were explored, including the ligand-to-metal charge transfer in complexation, modifications to reactive sites and activities with various reactive species, and higher hole-electron separation extents. In addition, the triplet excited state, singlet oxygen, and hydroxyl radical in LEV and LEV-Cu(II) with 1:1 molar ratio played pivotal roles in the transformation, contributing 20.77 %/20.02 %, 13.87 %/14.59 %, and 7.96 %/4.68 %, respectively. Furthermore, considering more FQs models, the inhibition of Cu(II) on the transformation was found to universally exist in ciprofloxacin, enoxacin, enrofloxacin, norfloxacin, ofloxacin and pefloxacin, and their multiple molecular descriptors were changed with a same tendency. This work provides a comprehensive understanding of the transformation of antibiotics within complex aqueous matrices, contributing to further estimation of antibiotics removal and ecological risks.