Understanding removal mechanisms of emerging organic contaminants in conventional activated sludge systems is of fundamental and engineering importance. In this study, we selected six environmentally relevant pharmaceuticals as target organic contaminants, namely, metronidazole (MTZ), bezafibrate (BZF), ibuprofen (IBP), sulfamethoxazole (SMX), carbamazepine (CBZ), and ciprofloxacin (CIP) for the mechanistic investigation for their removal. We demonstrated that sorption and biodegradation were the dominant pathways for contaminant removal, while volatilization and hydrolysis were negligible. The sorption removal process varied for the selected pharmaceuticals in the batch system. Then, first-order rate model was used to fit the biodegradation kinetics, and their first-order rate constants (k(bio)) were ranged from 3.67x10(-3) to 10.2 L g(-1) d(-1), in order of CBZ < CIP < SMX < MTZ < BZF < IBP. In order to elucidate the biodegradation mechanism, we calculated a total of twelve geometrical, electrostatic, and quantum chemical descriptors with density functional theory (DFT) approach. Then, correlation analysis was conducted to investigate kbio with these theoretical descriptors. Our results indicate that electrophilicity index (omega), a measure of electrophilic power, influences the biodegradation kinetics to the greatest extent. The omega corresponds to the process where the pharmaceutical molecule acts as an electrophile, adding electron density from a nucleophile. The combined experimental and theoretical results provide insight into the intrinsic nature of biodegradation of organic contaminants of emerging concern during conventional activated sludge treatment.