Improving biodegradation of pharmaceuticals during wastewater treatment is critical to control the release of emerging micropollutants to natural waters. In this study, biodegradation of six model pharmaceuticals was investigated at different initial concentrations in two discrete activated sludge systems, and moreover, the correlation was explored between the biodegradation rate and key molecular properties of the contaminants. First, the biodegradation rates of the pharmaceuticals were measured fitting a pseudo first−order kinetic model to the experimental kinetic data. The degradation rate constants (k bio ) were found to negatively correlate to the initial concentration of the chemicals, indicating an inhibitory effect on the microorganisms by the pharmaceuticals. Further examinations of the rate data against the key molecular properties of the pharmaceuticals revealed, for the first time, that the electrophilicity index (ω), a measure of electrophilic power, served as a better indicator of the biodegradability and predictive parameter for the k bio than the conventional log K OW (a measure of hydrophobicity) in the two discrete aerobic activated sludge systems. However, the correlation strength (goodness‒of‒fit) between ω and k bio deteriorated when the reactor turned from aerobic to anoxic and anaerobic conditions, suggesting that electron transfer from pharmaceutical molecules to enzymes was inhibited when dissolved oxygen was deficit or absent. Our results show that ω can potentially serve as a straightforward and robust indicator for predicting the biodegradability of pharmaceutical in conventional activated sludge processes.