This study explored the influence of structural characteristics of organic contaminants on the degradation during an advanced oxidation process (AOP). The target contaminants were acetaminophen (ACT), bisphenol A (BPA), and tetracycline (TC). The Fenton process was selected as the model process in which major reactive species of hydroxyl radicals in most AOPs are generated for target compound degradation. The optimal reagent concentration ratio was [Fe²⁺]/[H₂O₂] = 0.5 mM/0.5 mM in an acidic condition, resulting in 83.49%, 79.01%, and 91.37% removals of ACT, BPA, and TC, respectively. Contrarily, the mineralization rates were apparently lower compared to their respective removal efficiencies. Experimental observation also suggested that the aromatic structure was rather difficult to degrade since their unsaturated electron clouds would hinder the attack of hydroxyl radicals due to electric repulsion. The preferred attacking sites of an aromatic ring differ due to the functional groups and structure symmetry. However, the electrophilic attack of the hydroxyl radical is the major reaction for decomposing aliphatic structures of cyclic or branched organics, resulting in the highest removal and mineralization of TC among these three tested chemicals. In addition, an apparent removal of a contaminant may not necessarily reduce its toxic impact on the environment.