Ten common benzophenone-based UV filters (BPs), sharing the same basic structure and differing only in their substituents, were investigated with respect to their primary and ultimate biodegradability. This study was carried out in order to gain deeper insights into the relationship between structure and biodegradability. The primary biodegradation of the selected BPs was studied in river water at environmentally relevant concentrations (1 µg/L) while varying specific, crucial environmental conditions (aerobic, suboxic, supplementation of nutrients). For this purpose, both batch and column degradation tests were performed, which allowed a systematic study of the effects. Subsequently, the ultimate biodegradation, i.e. the potential to achieve full mineralization of BPs, was examined according to OECD guideline 301 F. The results indicate that mineralization is limited to derivatives in which both aromatic rings contain substituents. This hypothesis was supported by docking simulations showing systematic differences in the orientation of BPs within the active site of the cytochrome P450 enzyme. These differences in orientation correspond to the substitution pattern of the BPs. This study provides valuable insights for assessing the environmental hazards of this class of trace organic compounds.